WO2021059241A1 - Microbiome compositions and methods of treatment of atopic diseases - Google Patents

Abstract

This application discloses methods of treatment of atopic diseases comprising administering to a subject an effective amount of a composition comprising bacteria and methods of determining the likelihood of development of an atopic disease comprising determining the levels of various bacteria. Atopic disease includes asthma, food allergy, food sensitization, recurrent wheeze, allergic rhinitis, eczema, and/or atopic dermatitis. Bacteria include three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira. Roseburia, Blautia. Dorea, Parabacteroides or Ruminococcus for treating an atopic disease and two or more of said genera for the diagnostic method.

Description

MICROBIOME COMPOSITIONS AND METHODS OF TREATMENT OF ATOPIC DISEASES

DESCRIPTION

CROSS REFERENCE TO RELATED APPLICATIONS

[001] This application claims the benefit of priority of U.S. Patent Application No. 62/907,285 filed September 27, 2019, U.S. Patent Application No. 62/907,296 filed September 27, 2019, U.S. Patent Application No. 62/910,690 filed October 4, 2019, and U.S. Patent Application No. 62/927,283 filed October 29, 2019, the disclosures of which are incorporated herein by reference in their entireties. SEQUENCE LISTING

[002] The instant application contains a Sequence Listing which has been electronically submitted in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on September 25, 2020, is named 10109- 013WO1-SQL ST25 and is about 12KB in size.

FIELD

[003] This application relates to methods and bacterial compositions related to treatment of atopic diseases.

BACKGROUND

[004] Forty percent of the world’s population is sensitized to at least one environmental allergen and atopic diseases such as asthma, atopic dermatitis, and food allergy are among the most frequent health challenges faced by children today. Atopic conditions often manifest differently in similarly predisposed individuals and frequently co-occur within the same individual over time; a phenomenon best understood in the context of the “atopic march” (See Zheng T, et al. Allergy, Asthma Immunol Res. 3:67-73 (2011)). Atopic disease prevalence has risen dramatically in recent decades, and many atopic diseases have been considered incurable (See Stiemsma LT and Turvey SE. Allergy, Asthma Clin Immunol. 13:1-9 (2017) and Boutin RCT and Finlay BB. Curr Treat Options Allergy 2016:3:292-309 (2016)).

[005] Yet little is known about the underlying cause of many allergic diseases and no effective curative or preventative immunomodulatory therapies exist. However, recently multiple converging lines of evidence suggest that the gut microbiome may play a role in the etiology of atopic disease, especially during a critical window early in life. In fact, gut microbial dysbiosis in early life may precede atopic disease onset (See Stiemsma 2017, Boutin 2016, Arrieta MC, et al. Sci Transl Med. 7:307ral52 (2015) and BokulichNA, et al. Sci Transl Med. 8:343-82 (2016). In the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study, for instance, we previously observed that reductions in the relative abundance of four bacterial genera in the gut microbiota at three months of age were associated with the development of atopy and wheeze at age one year (See Arrieta MC, et al. Sci Transl Med. 7:307ral52 (2015)). Supplementation with representative bacteria from these genera was sufficient to reduce the severity of allergic airway inflammation in a humanized mouse model (Arrieta 2015).

[006] To date, most studies have focused on single atopic disease outcomes. As described herein, outcomes were assessed in the CHILD cohort to investigate the relationship between the early life gut microbiota and the development of several early life atopic conditions, with the goal of identifying specific ‘missing’ microbes involved in the natural history of the atopic march. Supplementation with ‘missing’ microbes in early life as a live biotherapeutic product (LBP) may represent a means of treating, curing, and/or preventing atopic diseases (See Stiemsma 2017, Boutin 2016, Arrieta 2015, and Gilbert JA, et al. Nature 535:94-103 (2016)). Thus, deliberate early-life supplementation with specific ‘missing’ immunomodulatory microbes represents an approach to the primary prevention of multiple human atopic diseases.

SUMMARY

[007] In accordance with the description, the present application provides, in part, methods and bacterial compositions to treat atopic diseases.

[008] In one aspect, the present application describes a method of treating one or more of an atopic disease in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus. This application also describes a method of treating one or more of an atopic disease in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, or Ruminococcus. [009] In some embodiments, the method comprises administering one or more bacteria of the genus Lachnospira. In some embodiments, the one or more bacteria of genus Lachnospira are chosen from Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, and Lachnospira rogosae. In some embodiments, the one or more bacteria of genus Lachnospira is Lachnospira eligens. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

[0010] In some embodiments, the method comprises administering one or more bacteria of the genus Faecalihacterium. In some embodiments, the one or more bacteria of genus Faecalihacterium is Faecalihacterium prausnitzii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalihacterium comprises SEQ ID NOs: 1-3. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalihacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

[0011] In some embodiments, the method comprises administering one or more bacteria of the genus Rosehuria. In some embodiments, the one or more bacteria of genus Rosehuria is Rosehuria hominis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Rosehuria comprises SEQ ID NOs: 13-14. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Rosehuria comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

[0012] In some embodiments, the method comprises administering one or more bacteria of the genus Blautia. In some embodiments, the one or more bacteria of genus Blautia is Blautia hydrogenotrophica. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

[0013] In some embodiments, the method comprises administering one or more bacteria of the genus Parahacteroides. In some embodiments, the one or more bacteria of genus Parahacteroides is Parahacteroides distasonis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises SEQ ID NO: 23. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23.

[0014] In some embodiments, the method comprises administering one or more bacteria of the genus Oscillospira. In some embodiments, the one or more bacteria of genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

[0015] In some embodiments, the method comprises administering one or more bacteria of the genus Dorea. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises SEQ ID NOs: 26. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 26.

[0016] In some embodiments, the method comprises administering one or more bacteria of the genus Tyzzerella.

[0017] In some embodiments, the method comprises administering one or more bacteria of the genus Ruminococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15-19 or 24-25. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

[0018] In some embodiments, the method comprises administering one or more bacteria of the genus Coprococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

[0019] In some embodiments, the atopic disease comprises asthma, food allergy, food sensitization, recurrent wheeze, allergic rhinitis, eczema, and/or atopic dermatitis. [0020] This application describes a method of treating atopic dermatitis in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus . This application also describes a method of treating atopic dermatitis in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, or Ruminococcus .

[0021] In some embodiments, the method comprises administering one or more bacteria of the genus Faecalibacterium. In some embodiments, the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3. In some embodiments, the 16s rRNA gene of the one or more bacteria of the genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

[0022] In some embodiments, the method comprises administering one or more bacteria of the genus Oscillospira. In some embodiments, the one or more bacteria of genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12. In some embodiments, the 16s rRNA gene of the one or more bacteria of the genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

[0023] In some embodiments, the method comprises administering one or more bacteria of the genus Roseburia. In some embodiments, the one or more bacteria of genus Roseburia is Roseburia hominis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

[0024] In some embodiments, the method comprises administering one or more bacteria of the genus Blautia. In some embodiments, the one or more bacteria of genus Blautia is Blautia hydrogenotrophica. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

[0025] In some embodiments, the method comprises administering one or more bacteria of the genus Parabacteroides. In some embodiments, the one or more bacteria of genus Parabacteroides is Parabacteroides distasonis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises SEQ ID NO: 23. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23.

[0026] In some embodiments, the method comprises administering one or more bacteria of the genus Dorea. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises SEQ ID NO: 26. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26.

[0027] In some embodiments, the method comprises administering one or more bacteria of the genus Tyzzerella.

[0028] In some embodiments, the method comprises administering one or more bacteria of the genus Ruminococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15-19 or 24-25. In some embodiments, the 16s rRNA gene of the one or more bacteria of the genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

[0029] In some embodiments, the method comprises administering one or more bacteria of the genus Coprococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10. In some embodiments, the 16s rRNA gene of the one or more bacteria of the genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

[0030] This application also describes a method of treating food allergy and/or food sensitization in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, or Ruminococcus. In addition, this application describes a method of treating food allergy and/or food sensitization in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, or Ruminococcus.

[0031] In some embodiments, the method comprises administering one or more bacteria of the genus Faecalibacterium. In some embodiments, the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3. In some embodiments, the 16s rRNA gene of the one or more bacteria of the genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

[0032] In some embodiments, the method comprises administering one or more bacteria of the genus Lachnospira. In some embodiments, the one or more bacteria of genus Lachnospira are chosen from Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, and Lachnospira rogosae. In some embodiments, the one or more bacteria of genus Lachnospira is Lachnospira eligens. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7. In some embodiments, the 16s rRNA gene of the one or more bacteria of the genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

[0033] In some embodiments, the method comprises administering one or more bacteria of the genus Oscillospira. In some embodiments, the one or more bacteria of genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

[0034] In some embodiments, the method comprises administering one or more bacteria of the genus Roseburia. In some embodiments, the one or more bacteria of genus Roseburia is Roseburia hominis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

[0035] In some embodiments, the method comprises administering one or more bacteria of the genus Blautia. In some embodiments, the one or more bacteria of genus Blautia is Blautia hydrogenotrophica. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

[0036] In some embodiments, the method comprises administering one or more bacteria of the genus Dorea. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises SEQ ID NO: 26. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26.

[0037] In some embodiments, the method comprises administering one or more bacteria of the genus Tyzzerella.

[0038] In some embodiments, the method comprises administering one or more bacteria of the genus Ruminococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15-19 or 24-25. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

[0039] In some embodiments, the method comprises administering one or more bacteria of the genus Coprococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

[0040] This application describes a method of treating recurrent wheeze in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, or Blautia. This application also describes a method of treating recurrent wheeze in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, or Roseburia.

[0041] In some embodiments, the method comprises administering one or more bacteria of the genus Faecalibacterium. In some embodiments, the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

[0042] In some embodiments, the method comprises administering one or more bacteria of the genus Lachnospira. In some embodiments, the one or more bacteria of genus Lachnospira are chosen from Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, and Lachnospira rogosae. In some embodiments, the one or more bacteria of genus Lachnospira is Lachnospira eligens. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

[0043] In some embodiments, the method comprises administering one or more bacteria of the genus Oscillospira. In some embodiments, the one or more bacteria of genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

[0044] In some embodiments, the method comprises administering one or more bacteria of the genus Roseburia. In some embodiments, the one or more bacteria of genus Roseburia is Roseburia hominis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

[0045] In some embodiments, the method comprises administering one or more bacteria of the genus Coprococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

[0046] In some embodiments, the method comprises administering one or more bacteria of the genus Blautia. In some embodiments, the one or more bacteria of genus Blautia is Blautia hydrogenotrophica. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

[0047] This application describes a method of treating atopy and wheeze in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, or Ruminococcus. This application also describes a method of treating atopy and wheeze in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Roseburia, Blautia, Parabacteroides, or Ruminococcus.

[0048] In some embodiments, the method comprises administering one or more bacteria of the genus Faecalibacterium. In some embodiments, the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

[0049] In some embodiments, the method comprises administering one or more bacteria of the genus Lachnospira. In some embodiments, the one or more bacteria of genus Lachnospira are chosen from Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, and Lachnospira rogosae. In some embodiments, the method comprises administering one or more bacteria of the genus Lachnospira. In some embodiments, the one or more bacteria of genus Lachnospira is Lachnospira eligens. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

[0050] In some embodiments, the method comprises administering one or more bacteria of the genus Rosehuria. In some embodiments, the one or more bacteria of genus Rosehuria is Rosehuria hominis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Rosehuria comprises SEQ ID NOs: 13-14. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Rosehuria comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

[0051] In some embodiments, the method comprises administering one or more bacteria of the genus Blautia. In some embodiments, the one or more bacteria of genus Blautia is Blautia hydrogenotrophica. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

[0052] In some embodiments, the method comprises administering one or more bacteria of the genus Parahacteroides. In some embodiments, the one or more bacteria of genus Parahacteroides is Parahacteroides distasonis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parahacteroides comprises SEQ ID NO: 23. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parahacteroides comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23.

[0053] In some embodiments, the method comprises administering one or more bacteria of the genus Ruminococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15-19 or 24-25. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25. [0054] In some embodiments, the method comprises administering one or more bacteria of the genus Coprococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

[0055] In some embodiments, the method comprises administering one or more bacteria of genus Oscillospira. In some embodiments, the one or more bacteria of the genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

[0056] In some embodiments, the atopic disease comprises asthma, food sensitization, food allergy, recurrent wheeze, allergic rhinitis, eczema, and/or atopic dermatitis.

[0057] In some embodiments, the bacterial composition comprises bacteria of two of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, or Ruminococcus.

[0058] In some embodiments, the bacterial composition comprises bacteria of three of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, or Ruminococcus.

[0059] In some embodiments, the bacterial composition comprises bacteria of four of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, or Ruminococcus.

[0060] In some embodiments, the bacterial composition comprises bacteria of five, six, seven, eight, or nine of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, or Ruminococcus .

[0061] In some embodiments, a method of treating one or more of an atopic disease in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, and Ruminococcus . [0062] In some embodiments, a method of treating one or more of an atopic disease in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, and Ruminococcus .

[0063] In some embodiments, a method of treating atopic dermatitis in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, and Ruminococcus.

[0064] In some embodiments, a method of treating atopic dermatitis in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, and Ruminococcus.

[0065] In some embodiments, a method of treating food sensitization and/or food allergy in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, and Ruminococcus.

[0066] In some embodiments, a method of treating food sensitization and/or food allergy in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, and Ruminococcus.

[0067] In some embodiments, a method of treating recurrent wheeze in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, and Blautia.

[0068] In some embodiments, a method of treating atopy and wheeze in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, and Ruminococcus. [0069] In some embodiments, a method of treating one or more of an atopic disease in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus.

[0070] In some embodiments, a method of treating one or more of an atopic disease in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, or Ruminococcus.

[0071] In some embodiments, a method of treating one or more of an atopic disease in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Anaerostipes, Eubacterium E, Instestinimonas, Flavonifractor, Roseburia, Ruminococcus B, Ruminococcus _E, Blautia, Blautia A, Tyzzerella, or Parabacteroides.

[0072] In some embodiments, method of treating one or more of an atopic disease in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera that produce short-chain fatty acids. In some embodiments, the short-chain fatty acids are chosen from butyrate, acetate, and propionate.

[0073] In some embodiments, the subject is a human infant or a pregnant female. In some embodiments, the human infant is one year old or younger. In some embodiments, the human infant is three months old or younger, 6 months old or younger, or 9 months old or younger. In some embodiments, the bacterial composition is administered prophylactically. In some embodiments, the bacterial composition is administered orally or rectally. In some embodiments, the bacterial composition is administered topically. In some embodiments, the bacterial composition is formulated as a liquid suspension.

[0074] In some embodiments, the administering results in an increase in the population of at least one bacteria of the genera comprised in the bacterial composition. In some embodiments, the increase is determined using quantitative polymerase chain reaction. In some embodiments, the increase is monitored by the detection of a metabolite present in a sample from said subject. [0075] This application describes abacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus , in combination with a carrier. This application also describes a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides , or Ruminococcus, in combination with a carrier.

[0076] In some embodiments, the bacterial composition comprises one or more bacteria of the genus Faecalibacterium. In some embodiments, the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

[0077] In some embodiments, the bacterial composition comprises one or more bacteria of the genus Lachnospira. In some embodiments, the one or more bacteria of genus Lachnospira are chosen from Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, and Lachnospira rogosae. In some embodiments, the one or more bacteria of genus Lachnospira is Lachnospira eligens. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

[0078] In some embodiments, the bacterial composition comprises one or more bacteria of the genus Oscillospira. In some embodiments, the one or more bacteria of genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

[0079] In some embodiments, the bacterial composition comprises one or more bacteria of the genus Roseburia. In some embodiments, the one or more bacteria of genus Roseburia is Roseburia hominis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

[0080] In some embodiments, the bacterial composition comprises one or more bacteria of the genus Blautia. In some embodiments, the one or more bacteria of genus Blautia is Blautia hydrogenotrophica. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

[0081] In some embodiments, the bacterial composition comprises one or more bacteria of the genus Parabacteroides. In some embodiments, the one or more bacteria of genus Parabacteroides is Parabacteroides distasonis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises SEQ ID NO: 23. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23.

[0082] In some embodiments, the bacterial composition comprises one or more bacteria of the genus Dorea. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises SEQ ID NO: 26. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26.

[0083] In some embodiments, the bacterial composition comprises one or more bacteria of the genus Tyzzerella.

[0084] In some embodiments, the bacterial composition comprises one or more bacteria of the genus Ruminococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15-19 or 24-25. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

[0085] In some embodiments, the bacterial composition comprises one or more bacteria of the genus Coprococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

[0086] In some embodiments, the bacteria are present in an amount effective for treating atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze, in a subject in need thereof. In some embodiments, the bacterial composition is for use in treating atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze, in a subject in need thereof. In some embodiments, the composition comprises bacteria of three, four, five, six, seven, eight, or nine of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus. In some embodiments, the bacteria are substantially pure. In some embodiments, the composition comprises bacteria of three, four, five, six, seven, eight, or nine of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, or Ruminococcus. In some embodiments, the bacteria are substantially pure.

[0087] This application also describes a method of determining the likelihood of development of atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze in a subject, comprising determining the levels of bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus in a sample from said subject, and comparing said levels to a reference or a healthy subject, wherein a decrease in the levels of the bacteria indicates the increased likelihood of development of atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze. In addition, this application describes a method of determining the likelihood of development of atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze in a subject, comprising determining the levels of bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, or Ruminococcus in a sample from said subject, and comparing said levels to a reference or a healthy subject, wherein a decrease in the levels of the bacteria indicates the increased likelihood of development of atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze. In some embodiments, the method comprises determining the levels of one or more bacteria of the genus Faecalibacterium. In some embodiments, the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

[0088] In some embodiments, the method comprises determining the levels of one or more bacteria of the genus Lachnospira. In some embodiments, the one or more bacteria of genus Lachnospira are Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, or Lachnospira rogosae. In some embodiments, the one or more bacteria of genus Lachnospira is Lachnospira eligens. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

[0089] In some embodiments, the method comprises determining the levels of one or more bacteria of the genus Oscillospira. In some embodiments, the one or more bacteria of genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii . In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%,

96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

[0090] In some embodiments, the method comprises determining the levels of one or more bacteria of the genus Roseburia. In some embodiments, the one or more bacteria of genus Roseburia is Roseburia hominis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

[0091] In some embodiments, the method comprises determining the levels of one or more bacteria of the genus Blautia. In some embodiments, the one or more bacteria of genus Blautia is Blautia hydrogenotrophica . In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

[0092] In some embodiments, the method comprises determining the levels of one or more bacteria of the genus Parabacteroides. In some embodiments, the one or more bacteria of genus Parabacteroides is Parabacteroides distasonis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises SEQ ID NO: 23. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23.

[0093] In some embodiments, the method comprises determining the levels of one or more bacteria of the genus Dorea. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises SEQ ID NO: 26. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26.

[0094] In some embodiments, the method comprises determining the levels of one or more bacteria of the genus Tyzzerella.

[0095] In some embodiments, the method comprises determining the levels of one or more bacteria of the genus Ruminococcus . In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15-19 or 24-25. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

[0096] In some embodiments, the method comprises determining the levels of one or more bacteria of the genus Coprococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

[0097] In some embodiments, the method further comprises determining the levels of a metabolite present in a sample from said subject. In some embodiments, the method further comprises administering an effective amount of a bacterial composition to a subject determined to have an increased likelihood of development of atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze.

[0098] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the claims.

[0099] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate one (several) embodiment(s) and together with the description, serve to explain the principles described herein.

DESCRIPTION OF THE SEQUENCES

[00100] The following table provides a listing of certain sequences referenced herein.

BRIEF DESCRIPTION OF THE DRAWINGS

[00101] Figures 1 A- 1 B provide information on patients with various atopic diseases and shows that atopic disease manifestations often co-occur at age 1 year. (A) Number of children with one or more of: atopy+wheeze, food sensitization, recurrent wheeze, and atopic dermatitis at age one year (n=316). (B) Odds ratios and 95% confidence intervals for children with at least two atopic disease manifestations (i.e., an atopic composite) assessed at age one year of being diagnosed with food allergy, atopic dermatitis, allergic rhinitis, asthma, or two or more of these conditions (allergic composite score) at age five years. Allergic composite is defined as two or more of asthma, allergic rhinitis, atopic dermatitis, and food sensitization at 5 years of age.

[00102] Figures 2A-2I present data on the risk of developing an allergic disease manifestation by age one year according to the bacterial alpha diversity (Shannon index) of the three-month gut microbiota determined by univariate logistic regression in (A) the full cohort included in this study, and in the cohort stratified by mode of delivery of (B) vaginal delivery or (C) Cesarean section delivery, (D) prenatal smoking exposure, (E) no prenatal smoking exposure, (F) female, (G) male, (H) parental asthma, and (I) no parental asthma. RW = recurrent wheeze; ARW = Atopy+recurrent wheeze; AW = atopy+wheeze; AD = atopic dermatitis. Odds ratios correspond to the risk of developing the associated clinical disease manifestation for each unit of increase in Shannon diversity

[00103] Figure 3 A and 3B provide an overview of the design and goals of the study, whereby bacterial taxa were nominated for inclusion in an atopic disease-preventative LBP using a series of complementary machine learning approaches to integrate clinical data with 16S rDNA amplicon sequencing data from stool samples collected at 3 months of age. (A) Fecal samples of subjects at 3 months of age are used to generate data on the composition of the gut microbiome in healthy subjects versus those who develop atopic diseases. This information can be used to formulate a bacterial composition (Rx) that can be used to decrease or inhibit atopic disease or allergic responses that would otherwise occur in patients at 1 year or 5 years of age, for example, in response to a variety of environmental factors. (B) A variety of methods were used to analyze amplicon-based microbiome data to nominate taxa enriched in healthy individuals versus individuals with an atopic disease manifestation at age one year. sOTU = sub-Operational Taxonomic Unit.

[00104] Figures 4A-4D provides data on relative abundance of genera within the three-month-old gut microbiota. These potential nomination for inclusion in an anti-allergic composite live biotherapeutic product by modeling methods in healthy subjects (left box plots of each pair shown for different genera). Data in subjects with atopic dermatitis (Figure 4A), food sensitization (Figure 4B), recurrent wheeze (Figure 4C), and atopy plus wheeze (Figure 4D) at one year of age are also shown. Taxa included in the final nomination for each clinical measurement assessed at one year are indicated with an arrow.

[00105] Figure 5 shows an overview of additional methods used to analyze amplicon-based microbiome data at both the sub-Operational Taxonomic Units (sOTU, strain level) and also at aggregated genus level to nominate taxa enriched in healthy individuals.

[00106] Figure 6 shows data quality control methods used. ROBPCA = robust principal component analysis.

[00107] Figure 7 presents prevalence of genera reported as potential nomination by modeling methods in healthy subjects (squares) and subjects with atopic dermatitis at 1 year (dots).

[00108] Figure 8 shows relative abundance of genera reported as potential nomination by modeling methods in healthy subjects (left box plot plots of each pair shown for different genera) and subjects with atopic dermatitis at 1 year (right box plot plots of each pair shown for different genera).

[00109] Figure 9 shows nominations for individual diseases and atopic composite at 1 year based on Greengenes database.

[00110] Figure 10 presents potential means by which release of immunomodulatory compounds from bacteria in the GI tract can lead to downregulation of an inflammatory response. SCFA = short-chain fatty acid (SCFA) metabolites; slgA = secreted IgA; DC = dendritic cell.

[00111] Figure 11 shows exemplary methodologies for assessment of Treg induction and measurement of inflammatory cytokines. Th = T helper; Treg = regulatory T cell.

[00112] Figures 12A-12B present data on IL-10 levels. Figure 12A shows exemplary methodologies for assessing IL-10 levels using PCMBs and DCs. Figure 12B shows production of IL-10, an anti-inflammatory cytokine, from PBMCs (left bars) and DCs (right bars), for each pair of bars. PBMCs = peripheral blood mononuclear cells.

[00113] Figure 13 shows immunomodulatory responses triggered by DC cell TLR5 receptor recognition of Lachnospira flagellins. These responses include a T-cell dependent anti-inflammatory pathway via Treg induction and B-cell production of secretory IgA-mediated immune exclusion. [00114] Figure 14 shows that acetate-induced DC production of retinoic acid elicits T-cell independent and T-cell dependent immune pathways. Human cohort studies have shown a reduction in abundance of Blautia in association with Crohn’s disease or graft versus host disease (GvHD). Blautia is also associated with reduction and delay of tumor growth in breast cancer mouse models. Blautia hydrogenotrophica is an acetogenic microbe and has been measured to contribute one-third of all acetate formed in the gut. The acetate receptor GPR43 is expressed on DCs, which produce retinoic acid and acetate binding results in the mediation of T-cell independent B cell slgA production.

[00115] Figure 15 shows that motility powered by multiple flagella enables Roseburia to penetrate and colonize the mucus layer, thereby increasing bioavailability of anti-inflammatory compounds and producing anti-inflammatory immune modulation. Proximity to the epithelia increases bioavailability of bacterial immunomodulatory compounds. Reduction in the abundance of Roseburia is associated with IBS/IBD and UC, with an increased presence associated with weight loss and reduced glucose tolerance. Co-occurrence with Faecalibacterium prausnitzii has been shown in many studies. In vivo work showed that treatment with Roseburia hominis leads to increased CD4⁺CD25⁺FoxP3⁺ Treg numbers in the lamina propria of mono-associated and conventional mice. In vitro work has also detected Roseburia colonization of the mucin layer.

[00116] Figure 16 shows that multiple cell components of Parabacteroides induce innate and adaptive immunomodulatory systems via upregulation of anti-inflammatory responses and downregulation of inflammatory responses. A transwell culture system can be used to monitor these effects in vitro. A reduced abundance of Parabacteroides has been seen in pediatric CF patients, in pediatric oncology patients receiving chemotherapy, and in pediatric patients suffering from acute viral gastroenteritis. Reduced co-occurrence with Oscillospira and Anaerostipes is seen in pediatric NAFLD, and co-occurrence with Roseburia and Oscillospira is protective against obesity and type-2 diabetes mellitus. In the dextran sulfate sodium (DSS)-colitis model, oral administration of Parabacteroides distasonis membrane and DNA induces multiple immunomodulatory pathways, including anti inflammatory changes, Treg proliferation, and antibodies to facilitate commensal immune protection. [00117] Figures 17A-17I show additional information on the bacterial genera, including fermentable substrates.

DESCRIPTION OF THE EMBODIMENTS

[00118] In the following detailed description, numerous specific details are set forth by way of examples in order to provide a thorough understanding of the relevant teachings. However, it should be apparent to those skilled in the art that the present teachings may be practiced without such details. In other instances, well known methods, procedures, components, and/or circuitry have been described at a relatively high-level, without detail, in order to avoid unnecessarily obscuring aspects of the present teachings.

I. Definitions

[00119] As used herein, “atopic disease” encompasses a range of diseases based on inappropriate immune responses. “Atopy” may refer to syndrome characterized by one or more atopic diseases. Atopic diseases are characterized by an immune response to an allergen that does not normally trigger an immune response. Atopic disease comprises asthma, food allergy, food sensitization, recurrent wheeze, allergic rhinitis, eczema, and/or atopic dermatitis, as well as other diseases characterized by an overactive immune response or a hyperallergic response. Atopy or an atopic disease may be associated with any type IgE-mediated allergic sensitization.

[00120] As used herein, “atopic dermatitis,” “eczema,” “atopic eczema,” or “dermatitis” refers to a disorder characterized by dry scaly patches on the skin, which may be very itchy.

[00121] As used herein, “food allergy” refers to an immune response triggered by a food or a substance in a food. Exemplary food allergies include an IgE- mediated allergy or a cell-mediated allergy.

[00122] As used herein, “food sensitization” refers to development of allergen-specific antibodies upon exposure to a specific food protein. A food sensitivity may be seen during the sensitization phase after exposure of a susceptible individual to a food allergen, after which the individual could later show an allergic reaction to the food allergen or the individual could develop oral tolerance. Children with food sensitization may or may not also be diagnosed as having a food allergy and vice versa. The methods described herein treat both food sensitization and food allergy irrespective of the diagnostic approach a clinician takes to evaluate and diagnose the child or irrespective of the type or level of reaction to a food exposure. [00123] As used herein, “allergic rhinitis” refers to a subject’s response to specific allergens, wherein the nose is affected. Allergic rhinitis may also be referred to as hay fever.

[00124] As used herein, “recurrent wheeze” refers to recurrent symptoms related to a narrowing or obstruction of the respiratory airways (i.e., wheezing). These symptoms may include high-pitched, whistling sounds during breathing. Recurrent wheeze may be associated with asthma. Recurrent wheeze may be characterized by 3 or more distinct episodes over the previous year.

[00125] As used herein, “asthma” refers to a condition in which the respiratory airways narrow, swell, and/or produce extra mucus. Asthma may cause difficulty breathing and trigger coughing, wheezing, and shortness of breath.

[00126] As used herein, “atopy and wheeze” refers to symptoms of atopic disease together with wheezing.

[00127] As used herein, the term “16S rRNA sequencing” refers to the sequencing of 16S ribosomal RNA (rRNA) gene sequences by using primers such as universal primers and/or species-specific primers to identify the bacteria present in a sample. 16S rRNA genes contain both highly conserved sites and hypervariable regions that can provide species-specific signature sequences useful for identification of bacteria. Such universal primers are well known in the art.

[00128] As used herein, the term “operational taxonomic unit” or “OTU” refers to group of bacterial sequences that differ among each other in <97% identity. A “type” or a plurality of “types” of bacteria includes an OTU or a plurality of different OTUs, and also encompasses differences in species, genus, family, or order of bacteria. The specific genetic sequence may be the 16S rRNA sequence or a portion of the 16S rRNA sequence or it may be a functionally conserved housekeeping gene found broadly across the eubacterial kingdom.

[00129] Specific taxa and changes in microbiota discussed herein can be detected using various methods, including without limitation quantitative PCR (qPCR) or high-throughput sequencing (e.g., shotgun metagenome sequencing) methods which detect over- and under-represented genes in the total bacterial population (e.g., Illumina-sequencing for community analysis; screening of microbial 16S ribosomal RNAs (16S rRNA), etc.), or transcriptomic or proteomic studies that identify lost or gained microbial transcripts or proteins within total bacterial populations, or metabolomics. See, e.g., U.S. Patent Publication No. 2010/0074872; Eckburg et al., Science, 2005, 308:1635-8; Costello et al., Science, 2009, 326:1694-7; Grice et al., Science, 2009, 324: 1190-2; Li et al., Nature, 2010, 464: 59-65; Bjursell et al., Journal of Biological Chemistry, 2006, 281:36269-36279; Mahowald et al.,

PNAS, 2009, 14:5859-5864; Wikoff et al., PNAS, 2009, 10:3698-3703.

[00130] The terms “treat” or “treatment” of a state, disorder or condition include: (1) preventing, delaying, or reducing the incidence and/or likelihood of the appearance of at least one clinical or sub-clinical symptom of the state, disorder or condition developing in a subject that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition; or (2) inhibiting the state, disorder or condition, i.e., arresting, reducing or delaying the development of the disease or a relapse thereof (in case of maintenance treatment) or at least one clinical or sub-clinical symptom thereof; or (3) relieving the disease, i.e., causing regression of the state, disorder or condition or at least one of its clinical or sub- clinical symptoms. The benefit to a subject to be treated is either statistically significant or at least perceptible to the patient or to the physician.

[00131] As used herein, the term “therapeutically effective amount” refers to the amount of a microbiota inoculum that, when administered to a subject for treating (e.g., preventing or ameliorating) a state, disorder or condition, is sufficient to result in such treatment. The “therapeutically effective amount” will vary depending, e.g., on the bacteria or analogues administered as well as the disease and physical conditions and responsiveness of the subject to be treated.

[00132] As used herein, the phrase “pharmaceutically acceptable” refers to molecular entities and compositions that are generally regarded as physiologically tolerable.

[00133] As used herein, the term “combination” of a bacterial composition and at least a second pharmaceutically active ingredient means at least two, but any desired combination of compounds can be delivered simultaneously or sequentially (e.g., within a 24-hour period). In some embodiments, a bacterial composition may be in combination with a prebiotic.

[00134] As used herein, the term “prebiotic” refers to an agent that increases the number and/or activity of one or more desired bacteria, enhancing their growth. Non-limiting examples of prebiotics useful in the methods of the present invention include fructooligosaccharides (e.g., oligofructose, inulin, inulin-type fructans), galactooligosaccharides, human milk oligosaccharides (HMO), Lacto-N- neotetraose, D-Tagatose, xylo-oligosaccharides (XOS), arabinoxylan- oligosaccharides (AXOS), N-acetylglucosamine, N-acetylgalactosamine, glucose, other five- and six-carbon sugars (such as arabinose, maltose, lactose, sucrose, cellobiose, etc.), amino acids, alcohols, resistant starch (RS), and mixtures thereof. See, e.g., Ramirez-Farias et al., BrJNutr 4: 1-10 (2008); Pool-Zobel and Sauer, JNutr 137:2580S-2584S (2007).

[00135] As used herein, “bacterial composition” refers to an agent comprising more than one substantially pure bacteria (i.e., a single isolate of live bacterial cells or an intentional mixture of single isolates, wherein the single isolate or mixture is at least 95% free of unwanted bacteria), or a mixture of desired bacteria, and may also include any additional components that can be administered to a mammal. Such compositions may also be referred to as a “bacterial inoculant” or “probiotic.” A bacterial composition may also be referred to as a “live biotherapeutic product” or “LBP.”

[00136] The terms “patient”, “individual”, “subject”, and “animal” are used interchangeably herein and refer to mammals, including, without limitation, human and veterinary animals (e.g., cats, dogs, cows, horses, sheep, pigs, etc.) and experimental animal models. The subject may be a human.

[00137] The term “carrier” refers to a diluent, adjuvant, excipient, or vehicle with which the compound is administered. Such pharmaceutical carriers can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. Water or aqueous solution saline solutions and aqueous dextrose and glycerol solutions are preferably employed as carriers, particularly for injectable solutions. Alternatively, the carrier can be a solid dosage form carrier, including but not limited to one or more of a binder (for compressed pills), a glidant, an encapsulating agent, a flavorant, and a colorant. Suitable pharmaceutical carriers are described in “ Remington's Pharmaceutical Sciences ” by E. W. Martin.

II. Bacterial Compositions

[00138] A number of bacterial genera can be nominated for inclusion in a bacterial composition based on the data and analysis presented in this application.

[00139] In some embodiments, a bacterial composition is for use in the treatment or prevention of one or more atopic disease. In some embodiments, the atopic disease comprises one or more of atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze, in a subject.

[00140] The naming conventions of a given bacterial genera may be different in different databases. In other words, the genera that comprises a given bacteria or group of bacteria may be named differently in different databases. In some embodiments, genus naming is based on the Greengenes database VI 3 8 or GTDB database v86. In some embodiments, the genera are those listed in Table 2 and/or Table 6.

[00141] As used herein, the genus “ Coprococcus ” may comprise

Anaerostipes and/or Eubacterium E.

[00142] As used herein, the genus Oscillospira may comprise Intestinimonas and/or Flavonifractor .

[00143] As used herein, the genus “ Ruminococcus ” may comprise

Ruminococcus B and/or Ruminococcus _E.

[00144] As used herein, the genus “ Dorea ” may comprise Coprococcus and/or Ruminococcus _B. In some embodiments, “ Tyzzerella ” is nominated in lieu of Dorea. As shown in Tables 2 and 6, certain sequences were classified differently in different databases.

[00145] As used herein, the genus “ Blautia ” may comprise Blautia and/or Blautia A .

[00146] In some embodiments, a bacterial composition comprises bacteria in combination with a carrier.

[00147] In some embodiments, a bacterial composition comprises bacteria of three of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, Ruminococcus.

[00148] In some embodiments, a bacterial composition comprises bacteria of three of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, Ruminococcus.

[00149] In some embodiments, a bacterial composition comprises bacteria of four of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, or Ruminococcus .

[00150] In some embodiments, a bacterial composition comprises bacteria of five, six, seven, eight, or nine of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, or Ruminococcus .

[00151] In some embodiments, the bacterial composition comprises one or more bacteria of the genus Faecalibacterium. In some embodiments, the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

[00152] In some embodiments, the bacterial compositions comprise one or more bacteria of the genus Lachnospira. In some embodiments, the one or more bacteria of genus Lachnospira are chosen from Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, and Lachnospira rogosae. In some embodiments, the one or more bacteria of genus Lachnospira is Lachnospira eligens. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

[00153] In some embodiments, the bacterial compositions comprise one or more bacteria of the genus Oscillospira. In some embodiments, the one or more bacteria of genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

[00154] In some embodiments, the bacterial compositions comprise one or more bacteria of the genus Roseburia. In some embodiments, the one or more bacteria of genus Roseburia is Roseburia hominis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14. [00155] In some embodiments, the bacterial compositions comprise one or more bacteria of the genus Blautia. In some embodiments, the one or more bacteria of genus Blautia is Blautia hydrogenotrophica. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

[00156] In some embodiments, the bacterial compositions comprise one or more bacteria of the genus Parabacteroides . In some embodiments, the one or more bacteria of genus Parabacteroides is Parabacteroides distasonis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises SEQ ID NO: 23. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23.

[00157] In some embodiments, the bacterial composition comprises one or more bacteria of the genus Dorea. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises SEQ ID NO: 26. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26.

[00158] In some embodiments, the bacterial composition comprises one or more bacteria of the genus Tyzzerella.

[00159] In some embodiments, the bacterial composition comprises one or more bacteria of the genus Ruminococcus . In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15- 19 or 24-25. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

[00160] In some embodiments, the bacterial composition comprises one or more bacteria of the genus Coprococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10. [00161] In some embodiments, the bacteria are present in an amount effective for treating atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze, in a subject in need thereof.

[00162] In some embodiments, the bacterial composition is for use in treating atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze, in a subject in need thereof.

[00163] In some embodiments, the composition comprises bacteria of three, four, five, six, seven, eight, or nine of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea,

Parabacteroides, or Ruminococcus . In some embodiments, the composition comprises bacteria of three, four, five, six, seven, eight, or nine of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, or Ruminococcus.

[00164] In some embodiments, the bacteria are substantially pure.

[00165] There may be a number of means by which a bacterial composition may affect atopic disease course or development.

A. Modulation of T-cell and B-cell Immune Pathways by Bacterial

Compositions

[00166] As shown in Figure 10, bacteria comprised in the microbiome near the GI epithelia can produce immunomodulatory compounds. Exemplary immunomodulatory compounds include short-chain fatty acid (SCFA) metabolites. A number of the nominated bacterial genera in this application belong to the class Clostridia, which are known producers of SCFAs (See Tables 3-4), and none of the nominated genera comprise known pathogens or pathobionts. Table 4 (below) presents additional information on SCFAs produced by the different nominated bacterial genera.

[00167] In some embodiments, one or more bacteria comprised in a bacterial composition produces one or more SCFAs. In some embodiments, the SCFAs are chosen from butyrate, acetate, and propionate.

[00168] As shown in Figure 10, SCFAs released by bacteria can mediate retinoic acid production by dendritic cells (DCs). Retinoic acid can mediate slgA-mediated immune exclusion of certain bacteria and also mediate downregulation of inflammatory responses by regulatory T cells (Tregs). [00169] In some embodiments, release of SCFAs by bacteria comprised in a bacterial composition leads to retinoic acid production by DCs. In some embodiments, release of SCFAs by bacteria comprised in a bacterial composition leads to soluble IgA (slgA)-mediated immune exclusion of certain bacteria. Via immune exclusion, slgA is known to both promote the clearance of antigens and pathogenic microorganisms from the intestinal lumen by blocking their access to epithelial receptors and also, importantly, downregulate pro-inflammatory responses in the gut (See Mantis et ak, Mucosal Immunol. 4(6): 603-611 (2011)). In some embodiments, release of SCFAs by bacteria comprised in a bacterial composition leads to downregulation of one or more inflammatory response. As atopic diseases are characterized by overactivity of a patient’s immune response, this downregulation may improve disease course or avoid disease developmental. The disease may be any atopic disease, including those described in this application.

[00170] In some embodiments, downregulation of the immune response is measured via Treg assays, cytokine assays from blood and/or epithelial cells, or SCFA quantification. Figure 11 presents some exemplary methodologies for assessment of Treg induction and measurement of inflammatory cytokines. In some embodiments, blood from a subject could be used to isolate DCs and T cells. In some embodiments, these DCs and T cells can be used to assess the activity of Tregs. In some embodiments, Treg activity can be assessed via flow cytometric analysis or multiplex cytokine panels.

[00171] Figure 12A also presents how IL-10 release can be used as a marker of induction of an anti-inflammatory response using blood samples. As an example of an anti-inflammatory cytokine response mediated by bacteria, supernatants from Faecalibacterium or Lachnospira from commercial sources or from healthy infants significantly increased production of IL-10, an anti-inflammatory cytokine, from PBMCs and DCs (Figure 12B).

B. Short-Chain Fatty Acid Metabolites (SCFAs) and Other

Mechanisms of Immune Modulation

[00172] SCFAs released by bacteria comprised in the gut microbiome has been hypothesized to produce anti-inflammatory immune modulation. Table 4 of this application (below) summarizes SCFAs and other mechanisms of anti inflammatory responses associated with these bacteria. [00173] These descriptions provide some representative mechanisms whereby presently claimed genera can produce anti-inflammatory responses, but these descriptions are not meant to limit the means by which the present bacterial compositions can potentially induce anti-inflammatory responses.

[00174] In some embodiments, Faecalibacterium prausnitzii can produce butyrate. Butyrate can induce Treg cell differentiation and to inhibit Thl7 and Th2 cell types. Further, butyrate can block NF-kappaB activation and IL-8 production. Butyrate can also enhance intestinal barrier function through increased expression of claudin-1 and zonula occludens-1 (ZO-1) and lead to occludin redistribution to increase anti-inflammatory behavior of gut epithelia (Wang et ah,

Dig Dis Sci. 57(12): 3126-35 (2012)). Butyrate is decreased in children with atopic dermatitis (Durack et ah, Nature Comm 9:707 (2018)), and butyrate administration in mice reduces airway inflammation (Thio et ah, J et al. Allergy Clin Immunol.

142(6): 1867-1883x12 (2018)).

[00175] In some embodiments, Lachnospira triggers an immunomodulatory response by DC TLR5 recognition of Lachnospira flagellins (Figure 13). This recognition can lead to T-cell dependent anti-inflammatory pathway via Treg induction and B-cell production of secretory IgA leading to immune exclusion (See Boyaka et al., J Immunol 199(1):9-16 (2017) and Corthesy Immunopharmacol Immunotoxicol. 31(2): 174-9 (2009)).

[00176] In some embodiments, production of acetate by Blautia can elicit T-cell-independent and T-cell dependent immunomodulation (See Bemalier et al., Archives Microbiology 166(3): 176-183 (1996)). Acetate can decrease both asthma risk and Th2 inflammation.

[00177] Human cohort studies have shown reduced abundance of Blautia in patients with Crohns disease or graft versus host disease (GvHD). Blautia is also associated with reduction and delay of tumor growth in a breast cancer mouse model. For example, Blautia hydrogenotrophica is an acetogenic microbe that contributes up to one-third of all acetate formed in the gut (Figure 14). Some acetate is formed in this way via fermentation of insoluble dietary fiber. The acetate receptor GPR43 is expressed on DCs that produce retinoic acid, and acetate binding to GPR43 mediates T-cell-independent production of slgA by B cells.

[00178] In some embodiments, the multiple flagella of Roseburia allows it to penetrate and colonize the mucosal layer, thereby increasing the bioavailability of anti-inflammatory compounds to enhance immune modulation (Figure 15). In human cohort studies, Roseburia abundance is reduced in patients with irritable bowel syndrome/inflammatory bowel disease (IBS/IBD) or ulcerative colitis (UC) (See Tamani-Shacoori et al., Future Medicine 12(2) (2017) and Tilg and Danese Gut 63(8): 1204-5 (2014)), and an increased presence of Roseburia is associated with weight loss and reduced glucose tolerance. Roseburia also often co-occurs with Faecalibacterium prausnitzii in humans. In vivo work showed that treatment with Roseburia hominis leads to increased CD4⁺CD25⁺FoxP3⁺ Treg numbers in the lamina propria of mono-associated and conventional mice. In vitro work has also detected Roseburia colonization of the mucin layer.

[00179] In some embodiments, Parabacteroides leads to decreased inflammatory responses (Figure 16). Reduced abundance of Parabacteroides has been shown in pediatric cystic fibrosis (CF) patients, pediatric oncology patients receiving chemotherapy, and patients suffering from acute viral gastroenteritis. Further, there is a reduced co-occurrence with Oscillospira, Coprococcus, and Anaerostipes in pediatric non-alcoholic fatty liver disease (NAFLD) patients, while co-occurrence with Roseburia and Oscillospira is protective against obesity and type-2 diabetes. In a dextran sulfate sodium (DSS)-colitis model, oral administration of Parabacteroides distasonis membrane and DNA induced anti-inflammatory cytokine release, Treg proliferation, and production of antibodies that facilitate commensal immune protection.

[00180] In some embodiments, Oscillospira is associated with protection from inflammatory diseases. Oscillospira co-occurs with other beneficial commensals. For example, there is reduced co-occurrence with Parabacteroides, Coprococcus and Anaerostipes in pediatric NAFLD patients, reduced occurrence in pediatric Crohns disease, and reduced co-occurrence with Roseburia and Parabacteroides in patients with obesity or type-2 diabetes. Oscillospira is also commonly associated with leanness (See Verdam et al., Obesity 21(12): E607-E615 (2013)).

[00181] Additional information on bacterial genera is included in Figures 17A-17I.

C. Formulations and Methods for Producing Compositions

[00182] The bacteria-containing formulations of the invention may comprise one or more prebiotics which promote growth and/or activity of the bacteria in the formulation. In some embodiments, a bacterial composition is administered in combination with a prebiotic. Non-limiting examples of prebiotic agents useful in the methods of the present invention include fructoobgosaccharides (e.g., oligofructose, inulin, inulin-type fructans), galactooligosaccharides, human milk oligosaccharides (HMO), Lacto-N-neotetraose, D-Tagatose, xylo-oligosaccharides (XOS), arabinoxylan-oligosaccharides (AXOS), N-acetylglucosamine, N- acetylgalactosamine, glucose, other five and six-carbon sugars (e.g., arabinose, maltose, lactose, sucrose, cellobiose, etc.), amino acids, alcohols, resistant starch (RS), fructose, melezitose, melibiose, pectin, polygalacturonic acid, glycerol, erythritol, glycogen, fiicose, raffmose, xylose, aescubn, and mixtures thereof. Additional prebiotic agents can be selected based on the knowledge of particular bacteria.

[00183] Methods for producing bacterial compositions of the invention may include three main processing steps, combined with one or more mixing steps. The steps are: organism banking, organism production, and preservation. For banking, the strains included in the bacterial compositions of the invention may be (1) isolated directly from a specimen or taken from a banked stock, (2) optionally cultured on a nutrient agar or broth that supports growth to generate viable biomass, and (3) the biomass optionally preserved in multiple aliquots in long-term storage. The bacterial suspension can be freeze-dried to a powder and titrated. After drying, the powder may be blended to an appropriate potency, and mixed with other cultures and/or a filler such as microcrystalline cellulose for consistency and ease of handling, and the bacterial composition formulated as provided herein.

[00184] The relative abundance of the taxa may comprise a method selected from the group consisting of quantitative polymerase chain reaction (qPCR), sequencing of bacterial 16S rRNA, shotgun metagenome sequencing, and metabolomics.

[00185] In accordance with the present invention there may be numerous tools and techniques within the skill of the art for producing a bacterial composition, such as those commonly used in molecular biology, pharmacology, and microbiology. Such tools and techniques are described in detail in e.g., Sambrook et al. (2001) Molecular Cloning: A Laboratory Manual. 3rd ed. Cold Spring Harbor Laboratory Press: Cold Spring Harbor, N.Y.; Ausubel et al. eds. (2005) Current Protocols in Molecular Biology. John Wiley and Sons, Inc.: Hoboken, N.J.; Bonifacino et al. eds. (2005) Current Protocols in Cell Biology. John Wiley and Sons, Inc.: Hoboken, N.J.; Coligan et al. eds. (2005) Current Protocols in Immunology,

John Wiley and Sons, Inc.: Hoboken, N.J.; Coico et al. eds. (2005) Current Protocols in Microbiology, John Wiley and Sons, Inc.: Hoboken, N.J.; Coligan et al. eds. (2005) Current Protocols in Protein Science, John Wiley and Sons, Inc.: Hoboken, N.J.; and Enna et al. eds. (2005) Current Protocols in Pharmacology, John Wiley and Sons,

Inc.: Hoboken, N.J.

[00186] In some non-limiting embodiments, the compositions of the invention are formulated as pharmaceutical preparations for oral, topical, nasal, rectal, mucosal, sublingual, or nasal administration. In some embodiments, the formulation is a slow release formulation. In some embodiments, the compositions are formulated as medical foods, nutritional or dietary supplements, food products, or beverage products.

III. Methods of Treatment

[00187] In some embodiments, a bacterial composition administered for the treatment or prevention of an atopic disease in a subject. In some embodiments, the atopic disease comprises asthma, food allergy, food sensitization, recurrent wheeze, allergic rhinitis, eczema, and/or atopic dermatitis.

[00188] In some embodiments, the human infant is one year old or younger. In some embodiments, the human infant is three months old or younger, 6 months old or younger, or 9 months old or younger. In some embodiments, the infant is a newborn (less than 1 month old) or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 months old, or one year old.

[00189] In some embodiments, the bacterial composition is administered prophylactically.

[00190] In some embodiments, the administering results in an increase in the population of at least one bacteria of the genera comprised in the bacterial composition. In some embodiments, the increase is determined using quantitative polymerase chain reaction. In some embodiments, the increase is monitored by the detection of a metabolite present in a sample from said subject. In some embodiments, the metabolite is a SCFA.

[00191] A bacterial composition can be administered to any body part colonized in the subject, including but not limited to, mouth, nasal mucosa, skin, etc. Non-limiting examples of suitable routes of administration of bacterial compositions include oral (e.g., swabbing or via feeding tube or baby bottle or applied to the mother’s breast topically before or during nursing), topical, rectal (e.g., by enema), mucosal, sublingual, nasal, and via naso/oro-gastric gavage. If a reproducible and measured dose is desired, the bacteria can be administered by a rumen cannula.

[00192] In some embodiments, the bacterial composition is administered orally or rectally. In some embodiments, the bacterial composition is administered topically. In some embodiments, the bacterial composition is formulated as a liquid suspension.

A. Treatment of Atopic Disease

[00193] In some embodiments, a method of treating one or more of an atopic disease in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus.

[00194] In some embodiments, a method of treating one or more of an atopic disease in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, or Ruminococcus.

[00195] In some embodiments, a method of treating one or more of an atopic disease in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, and Ruminococcus .

[00196] In some embodiments, a method of treating one or more of an atopic disease in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, and Ruminococcus.

[00197] In some embodiments, a method of treating one or more of an atopic disease in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus. [00198] In some embodiments, a method of treating one or more of an atopic disease in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, or Ruminococcus.

[00199] In some embodiments, a method of treating one or more of an atopic disease in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Anaerostipes, Eubacterium E, Instestinimonas, Flavonifractor, Roseburia, Ruminococcus B, Ruminococcus _E, Blautia, Blautia A, Tyzzerella, or Parabacteroides.

[00200] In some embodiments, the method comprises administering one or more bacteria of the genus Lachnospira. In some embodiments, the one or more bacteria of genus Lachnospira are chosen from Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, and Lachnospira rogosae. In some embodiments, the one or more bacteria of genus Lachnospira is Lachnospira eligens. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

[00201] In some embodiments, the method comprises administering one or more bacteria of the genus Faecalibacterium. In some embodiments, the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

[00202] In some embodiments, the method comprises administering one or more bacteria of the genus Roseburia. In some embodiments, the one or more bacteria of genus Roseburia is Roseburia hominis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14. [00203] In some embodiments, the method comprises administering one or more bacteria of the gen genus era Blautia. In some embodiments, the one or more bacteria of genus Blautia is Blautia hydrogenotrophica . In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

[00204] In some embodiments, the method comprises administering one or more bacteria of the genus Parabacteroides. In some embodiments, the one or more bacteria of genus Parabacteroides is Parabacteroides distasonis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises SEQ ID NO: 23. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23.

[00205] In some embodiments, the method comprises administering one or more bacteria of the genus Oscillospira. In some embodiments, the one or more bacteria of genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

[00206] In some embodiments, the method comprises administering one or more bacteria of the genus Dorea. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises SEQ ID NO: 26. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26.

[00207] In some embodiments, the method comprises administering one or more bacteria of the genus Tyzzerella.

[00208] In some embodiments, the method comprises administering one or more bacteria of the genus Ruminococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15- 19 or 24-25. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

[00209] In some embodiments, the method comprises administering one or more bacteria of the genus Coprococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

[00210] In some embodiments, the atopic disease comprises asthma, food allergy, food sensitization, recurrent wheeze, allergic rhinitis, eczema, and/or atopic dermatitis. In some embodiments, the atopic disease comprises more than one of asthma, food allergy, food sensitization, recurrent wheeze, allergic rhinitis, eczema, or atopic dermatitis.

B. Treatment of Atopic Dermatitis

[00211] In some embodiments, a method of treating atopic dermatitis in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus.

[00212] In some embodiments, a method of treating atopic dermatitis in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, or Ruminococcus.

[00213] In some embodiments, a method of treating atopic dermatitis in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, and Ruminococcus.

[00214] In some embodiments, a method of treating atopic dermatitis in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, and Ruminococcus. [00215] In some embodiments, the method comprises administering one or more bacteria of the genus Faecalibacterium. In some embodiments, the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

[00216] In some embodiments, the method comprises administering one or more bacteria of the genus Oscillospira. In some embodiments, the one or more bacteria of genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

[00217] In some embodiments, the method comprises administering one or more bacteria of the genus Roseburia. In some embodiments, the one or more bacteria of genus Roseburia is Roseburia hominis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

[00218] In some embodiments, the method comprises administering one or more bacteria of the genus Blautia. In some embodiments, the one or more bacteria of genus Blautia is Blautia hydrogenotrophica. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

[00219] In some embodiments, the method comprises administering one or more bacteria of the genus Parabacteroides. In some embodiments, the one or more bacteria of genus Parabacteroides is Parabacteroides distasonis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises SEQ ID NO: 23. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23.

[00220] In some embodiments, the method comprises administering one or more bacteria of the genus Dorea. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises SEQ ID NO: 26. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26.

[00221] In some embodiments, the method comprises administering one or more bacteria of the genus Tyzzerella.

[00222] In some embodiments, the method comprises administering one or more bacteria of the genus Ruminococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15- 19 or 24-25. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

[00223] In some embodiments, the method comprises administering one or more bacteria of the genus Coprococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

C. Treatment of Food Sensitization and/or Food Allergy

[00224] In some embodiments, a method of treating food sensitization and/or food allergy in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, or Ruminococcus. In some embodiments, a method of treating food sensitization and/or food allergy in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus,

Oscillospira, Roseburia, Blautia, Tyzzerella, or Ruminococcus.

[00225] In some embodiments, a method of treating food sensitization and/or food allergy in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, and Ruminococcus.

[00226] In some embodiments, a method of treating food sensitization and/or food allergy in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, and Ruminococcus.

[00227] In some embodiments, the method comprises administering one or more bacteria of the genus Faecalibacterium. In some embodiments, the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

[00228] In some embodiments, the method comprises administering one or more bacteria of the genus Lachnospira. In some embodiments, the one or more bacteria of genus Lachnospira are chosen from Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, and Lachnospira rogosae. In some embodiments, the one or more bacteria of genus Lachnospira is Lachnospira eligens. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

[00229] In some embodiments, the method comprises administering one or more bacteria of the genus Oscillospira. In some embodiments, the one or more bacteria of genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

[00230] In some embodiments, the method comprises administering one or more bacteria of the genus Roseburia. In some embodiments, the one or more bacteria of genus Roseburia is Roseburia hominis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

[00231] In some embodiments, the method comprises administering one or more bacteria of the genus Blautia. In some embodiments, the one or more bacteria of genus Blautia is Blautia hydrogenotrophica. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

[00232] In some embodiments, the method comprises administering one or more bacteria of the genus Dorea. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises SEQ ID NO: 26. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26.

[00233] In some embodiments, the method comprises administering one or more bacteria of the genus Tyzzerella.

[00234] In some embodiments, the method comprises administering one or more bacteria of the genus Ruminococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15- 19 or 24-25. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

[00235] In some embodiments, the method comprises administering one or more bacteria of the genus Coprococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10. D. Treatment of Recurrent Wheeze

[00236] In some embodiments, a method of treating recurrent wheeze in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, or Blautia.

[00237] In some embodiments, a method of treating recurrent wheeze in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, or Roseburia.

[00238] In some embodiments, a method of treating recurrent wheeze in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, and Blautia.

[00239] In some embodiments, the method comprises administering one or more bacteria of the genus Faecalibacterium. In some embodiments, the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

[00240] In some embodiments, the method comprises administering one or more bacteria of the genus Lachnospira. In some embodiments, the one or more bacteria of genus Lachnospira are chosen from Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, and Lachnospira rogosae. In some embodiments, the one or more bacteria of genus Lachnospira is Lachnospira eligens. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

[00241] In some embodiments, the method comprises administering one or more bacteria of the genus Oscillospira. In some embodiments, the one or more bacteria of genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

[00242] In some embodiments, the method comprises administering one or more bacteria of the genus Roseburia. In some embodiments, the one or more bacteria of genus Roseburia is Roseburia hominis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

[00243] In some embodiments, the method comprises administering one or more bacteria of the genus Coprococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

[00244] In some embodiments, the method comprises administering one or more bacteria of the genus Blautia. In some embodiments, the one or more bacteria of genus Blautia is Blautia hydrogenotrophica. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

E. Treatment of Atopy and Wheeze

[00245] In some embodiments, a method of treating atopy and wheeze in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, or Ruminococcus.

[00246] In some embodiments, a method of treating atopy and wheeze in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Roseburia, Blautia, Parabacteroides, or Ruminococcus. [00247] In some embodiments, a method of treating atopy and wheeze in a subject in need thereof comprises administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, and Ruminococcus

[00248] In some embodiments, the method comprises administering one or more bacteria of the genus Faecalibacterium. In some embodiments, the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

[00249] In some embodiments, the method comprises administering one or more bacteria of the genus Lachnospira. In some embodiments, the one or more bacteria of genus Lachnospira are chosen from Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, and Lachnospira rogosae. In some embodiments, the method comprises administering one or more bacteria of the genus Lachnospira. In some embodiments, the one or more bacteria of genus Lachnospira is Lachnospira eligens. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

[00250] In some embodiments, the method comprises administering one or more bacteria of the genus Roseburia. In some embodiments, the one or more bacteria of genus Roseburia is Roseburia hominis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

[00251] In some embodiments, the method comprises administering one or more bacteria of the genus Blautia. In some embodiments, the one or more bacteria of genus Blautia is Blautia hydrogenotrophica. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

[00252] In some embodiments, the method comprises administering one or more bacteria of the genus Parabacteroides. In some embodiments, the one or more bacteria of genus Parabacteroides is Parabacteroides distasonis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises SEQ ID NO: 23. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23.

[00253] In some embodiments, the method comprises administering one or more bacteria of the genus Ruminococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15- 19 or 24-25. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

[00254] In some embodiments, the method comprises administering one or more bacteria of the genus Coprococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

[00255] In some embodiments, the method comprises administering one or more bacteria of genus Oscillospira.

[00256] In some embodiments, the one or more bacteria of the genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

IV. Methods of Diagnosis

[00257] In some embodiments, a method of determining the likelihood of development of an atopic disease in a subject is determined by measuring the levels of bacteria. [00258] In some embodiments, a method of determining the likelihood of development of atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze in a subject, comprises determining the levels of bacteria of two or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus in a sample from said subject. In some embodiments, a method of determining the likelihood of development of atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze in a subject, comprises determining the levels of bacteria of two or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, or Ruminococcus in a sample from said subject. In some embodiments, said levels are compared to a reference or a healthy subject. In some embodiments, a decrease in the levels of the bacteria indicates the increased likelihood of development of atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze.

[00259] In some embodiments, the method of comprises determining the levels of one or more bacteria of the genus Faecalibacterium. In some embodiments, the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

[00260] In some embodiments, the method comprises determining the levels of one or more bacteria of the genus Lachnospira. In some embodiments, the one or more bacteria of genus Lachnospira are Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, or Lachnospira rogosae. In some embodiments, the one or more bacteria of genus Lachnospira is Lachnospira eligens. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

[00261] In some embodiments, the method comprises determining the levels of one or more bacteria of the genus Oscillospira. In some embodiments, the one or more bacteria of genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii . In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%,

96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

[00262] In some embodiments, the method comprises determining the levels of one or more bacteria of the genus Roseburia. In some embodiments, the one or more bacteria of genus Roseburia is Roseburia hominis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

[00263] In some embodiments, the method comprises determining the levels of one or more bacteria of the genus Blautia. In some embodiments, the one or more bacteria of genus Blautia is Blautia hydrogenotrophica. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

[00264] In some embodiments, a method comprises determining the levels of one or more bacteria of the genus Parabacteroides. In some embodiments, the one or more bacteria of genus Parabacteroides is Parabacteroides distasonis. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises SEQ ID NO: 23. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23.

[00265] In some embodiments, a method comprises determining the levels of one or more bacteria of the genus Dorea. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises SEQ ID NO: 26. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Dorea comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26. [00266] In some embodiments, a method comprises determining the levels of one or more bacteria of the genus Tyzzerella.

[00267] In some embodiments, a method comprises determining the levels of one or more bacteria of the genus Ruminococcus . In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15-19 or 24-25. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

[00268] In some embodiments, a method comprises determining the levels of one or more bacteria of the genus Coprococcus. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10. In some embodiments, the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

[00269] In some embodiments, a method further comprises determining the levels of a metabolite present in a sample from said subject. In some embodiments, the metabolite is a SCFA.

[00270] In some embodiments, method further comprises administering an effective amount of a composition to a subject determined to have an increased likelihood of development of atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze.

EXAMPLES

Example 1. Description of CHILD Study and Sample Collection

[00271] The CHILD study investigated the prevalence of different bacterial genera in children using fecal samples. It was hypothesized that a common set of microbes in the early life gut microbiota of a precisely defined cohort of “healthy” children would be associated with a decreased risk of atopic dermatitis, food and allergen sensitization, and recurrent wheeze (one of the strongest risk factors for asthma) at age one year. The experimental design and methods of the CHILD study are summarized in Figure 3A.

[00272] DNA from fecal samples collected at three months of age from CHILD cohort participants was extracted using the MO BIO PowerMag Soil DNA Isolation Kit. The V4 hypervariable region of the 16S rRNA gene was amplified by PCR using universal bacterial primers (V4-515f: V4-806r) and pooled PCR amplicons were subjected to paired-end sequencing on the Illumina MiSeq platform.

[00273] The CHILD cohort recruited a total of 3,455 pregnant women aged 18 years or older (19 or older in Vancouver) from four cities across Canada (see Subbarao P. et al., Thorax 70:998-1000 (2015) and Moraes TJ et al., Paediatr Perinat Epidemiol. 29:84-92 (2015) for a detailed description). Infants bom after 34 weeks of gestation with no congenital abnormalities were eligible and 3054 (93.6%) remained in the study at 5 years. The current analysis was based on 456 children for whom fecal microbiome data at three months of age had been analyzed and 1-, 3-, and 5 -year clinical outcomes data were available.

[00274] The CHILD cohort prospectively followed children prenatally to age 5 years and collected a comprehensive array of clinical objective measurements and assessments, allowing the diagnosis of atopic diseases including asthma, allergic sensitization, wheeze, allergic rhinitis, and atopic dermatitis (or eczema). The health status of the CHILD study subjects was recorded using a combination of questionnaires and structured in-person clinical assessments at 11 time points over a period of five years after birth.

[00275] Children were diagnosed with IgE-mediated allergic sensitization (also referred to as atopy) based on skin prick testing to multiple common food and environmental inhalant allergens, using > 2 mm average wheal size as indicating a positive test relative to the negative control. Allergens tested at the one-year visit were German cockroach, Alternaria alternata, house dust mites ( Dermatophagoides psteronys sinus and Dermatophagoides farnae), cat hair, dog epithelium, cow’s milk, peanut, egg white and soybean. Glycerin and histamine served as the negative and positive controls, respectively. Additional allergens tested at three- and five-year visits were Cladosporium, tree mix, grass mix, Aspergillus fumigatus, weed mix, ragweed mix and penicillium mix. Food sensitization was defined at ages one, three, and five years after birth based on skin prick test measurements to the following foods: eggs, peanut, milk, and soybean.

[00276] Atopic dermatitis was diagnosed at ages one, three, and five years after birth based on a clinical assessment by a CHILD healthcare professional using the UK Working Party criteria (See Dharma C, Paediatr Perinat Epidemiol 32:556-67 (2018)). [00277] Recurrent wheeze (RW) was defined at ages one, three, and five years after birth if the subject reports two or more episodes of wheeze within the preceding year as indicated by the response to the Child Health Questionnaire or clinical assessment. Asthma was diagnosed at ages 3 and 5 years based on a study pediatrician or healthcare professional’s response to the question: “In your opinion, does this child have asthma? (Yes / Possible / No)”. The pediatric asthma specialist or the highly trained health care professional working under their supervision conducted a structured interview with the accompanying parent or guardian identifying symptoms consistent with asthma, namely recurrent wheeze and coughing without a cold, and noted any physical findings. Asthma was considered definite if the parent reported physician-diagnosed asthma, or use of a bronchodilator prescribed by a physician for episodes of coughing or wheezing, or use of a prescribed daily controller medication, or frequent wheezing (3 or more distinct episodes over the previous year) with no alternative diagnosis. Atopy was not essential to the diagnosis but, together with parental history, weighted the likelihood of diagnosing recurrent wheezing as definite asthma. Possible asthma was recorded if there were less frequent episodes of wheeze or coughing without colds, and no report of medication use. Only definite cases of asthma (“Yes” to the initial interview question) were considered as cases for the purposes of the present study.

[00278] Healthy subjects (n=140 with fecal samples available; n=l 12 with sequencing data after processing) were defined as CHILD study subjects who were persistently negative at all time for atopic disease. Given that atopic diseases are dynamic and often progressive, healthy controls were defined in this study as children who were negative for all signs and symptoms of allergic disease up to age five years. Specifically, healthy controls were negative for all of the following: recurrent wheeze at age one, three, or five years; asthma at age three years; atopic dermatitis at age one, three, or five years; food allergy at age three or five years; allergic rhinitis at age three or five years; and sensitization to food or inhalant allergens as assessed by a positive skin prick test at ages one, three, or five years.

[00279] Figure 1A presents information on the atopic diagnoses at one year of age of subjects in the CHILD study (Figure 1A). Figure IB presents the association of a positive allergic composite index (defined as having two or more atopic outcomes (AD, FS, RW or AW) at age one year) with higher rates of allergic diseases at age five years. Children with a positive atopic composite score at 1 year of age are at increased risk of allergic disease at age 5 years. Therefore, Figure IB suggests that atopic manifestations at 1 year of age predict allergic outcomes at 5 years of age. Thus, outcomes at 1 year of age can be used as a proxy for later allergic disease outcomes and represent a realistic target for clinical trials.

[00280] Additional information on subjects included in CHILD study is also presented in Figures 2A-2I, including aspects of environmental or family history related to atopic diseases.

[00281] Thus, the CHILD study indicates that atopic phenotypes at 1 year of age predict those at 5 years of age.

Example 2. Sequence Processing and Statistical Analysis

[00282] Demultiplexed fastq-fdes were processed in QIIME2 (Bolyen E Nat Biotechnol. 37:852-857 (2019)) to generate sub-Operational Taxonomic Units (sOTUs) as recommended by the deblur workflow (www.github.com/biocore/deblur) (See Amir A et ak, Am Soc Microbiol. 2:e00191-16 (2017)). The taxonomic assignment of the sOTUs was performed using the Greengenes database (version 13 8) (www.greengenes.secondgenome.com/downloads/database/13_8) (See DeSantis TZ et ak, Appl Environ Microbiol. 72:5069-72 (2006)). All downstream microbiome data analyses were performed in the statistical software package R version 3.3.0, using packages including phyloseq

(www.github.com/joey711/phyloseq; McMurdie PJ PLoS One. 8(4): e61217 (2013)), randomForest (www.stat.berkeley.edu/~breiman/RandomForests/; Breiman L. Mach Learn. 45:5-32 (2001)), and mixOmicsCaret

(www.github.com/jonathanth/mixOmicsCaret; See Rohart F et ak, PloS Comput Biol 13(11): el005752 (2017)) and Chung D and Keles S Stat Appl Genet Mol Biol.

9(1): 17 (2010)). The maturity index of the gut microbiota was computed for each sample using previously published methods (See Subramanian S, et ak Nature 510:417-21 (2014) and Stokholm J, et ak Nat Commun. 9:141 (2018)) to compare overall differences in the gut microbiota composition between healthy controls and cases. The overall data analysis workflow is described in Figure 3B.

[00283] The Data QC step defined the healthy cohort for all clinical measurements and removed rare sOTUs and low-quality reads. The microbiome data were examined at aggregated genus level given the taxonomic resolution afforded by 16S sequencing. In order to correct for sequencing variation across the samples and sequencing batch effects, the microbiome data were rarefied and percentile normalized, respectively. Additionally, raw microbiome data along with sequencing batch and depth information were used as additional parameters for some methods.

[00284] Three distinct differential abundance methods were used to nominate taxa that were significantly and differentially abundant between individuals with a positive clinical measurement and healthy individuals. Differences in the relative abundances at the genus level were analyzed using a number of differential abundance tests present in the R package DATest

(www.github.com/Russel88/DAtest; See Russel J et al. bioRxiv 7:93 (2018)) including t-test, Wilcoxon rank-sum test, linear regressions, limma, SAMseq, edgeR, DESeq2, metagenome Seq, and ANCOM. The importance of differentially abundant taxa (at genus level) for differentiating individuals with and without disease was also determined using the sparse Partial Least Square - Discriminant Analysis (sPLS-DA, See Chung 2010) and random forest classification. An optimized number of input variables were selected using repeated 10-fold cross-validation of the Area Under the Curve (AUC) statistic to avoid overfitting.

[00285] Subsequently nominated taxa for each condition were further filtered for their prevalence greater than 15% in the healthy children and relative abundances greater than 0.2% (Figures 4A-4D). A statistical significance level of 0.05 and an AUC cut-off of greater than 0.6 were used in all analyses.

Example 3. Nomination for Clinical Measurements

[00286] Using the above-mentioned methods, the microbiome data collected at three months of age was used to nominate taxa that are associated with protection against clinical measures/phenotypes at age one year.

[00287] A series of complementary machine learning approaches to integrate comprehensive clinical data in the CHILD cohort with 16S rDNA amplicon sequencing data from stool samples collected at three months of age (n=654). Using this approach, a consortium of microbes was nominated in the infant gut as candidates for inclusion in a live biotherapeutic product (LBP) that can be tested for its potential to prevent the onset of a variety of frequently co-occurring atopic disease manifestations.

[00288] The clinical measurements for which the method was applied were atopic dermatitis, food sensitization, recurrent wheeze, and atopy plus wheeze. The nominated genera for each clinical measure are listed in Table 1, showing nominated genera from the three-month-old for each clinical measurement assessed at age one year.

[00289] There is a significant overlap in the nominated genera for the individual clinical measurements. These genera were combined into a single nomination for a composite atopic disease which is defined as having two or more of the clinical measurements: atopic dermatitis, food sensitization, recurrent wheeze, and atopy plus wheeze. Taxa included in the final nomination were further refined by including only those present at greater relative abundance in controls relative to cases for at least three of the four clinical phenotypes assessed, regardless of whether this difference was statistically significant.

[00290] The sequences of the nominated genera were also mapped to the Genomic Taxonomy Database (version 86) (www.gtdb.ecogenomic.org/, See Parks DH, et al. Nat Biotechnol 36:996-1004 (2018)), and their corresponding genera are listed in Table 2. While the Greengenes database is relatively older, the GTDB database uses a very recent, up-to-date database that may allow for more precise annotation. Further, the GTDB database may have assigned new formal names to genera previously awaiting final classification.

Square brackets ([]) around a genus indicates that NCBI Taxonomy has determined that some species have been misclassified by incorrectly being placed in a higher taxonomic rank. For example, a genus surrounded in square brackets indicates that the genus may likely be misclassified in a given database, but a new formal classification has not yet been provided by this database.

[00291] Consistent with previous studies, differences in global measures of gut microbiota diversity and maturity at three months of age were observed between infants who remained healthy and those with an allergic diagnosis at age one year (Figures 4A-4D). To identify specific key microbes involved in driving these effects and having the potential to be administered as therapeutics, machine learning techniques were applied on 16S rRNA amplicon sequence data taxonomically annotated to the genus level to identify specific bacterial genera that differed in relative abundance between healthy children (n=l 12) and children who developed atopic dermatitis (AD) (n=l 11), food sensitization (FS) (n=139), recurrent wheeze (RW) (n=142), and/or atopy plus wheeze (AW) (n=45) at one year of age (Figure 1A; n=456 with processed sequencing data and data available on all four clinical indications at age one year).

[00292] Clinical trials designed to test the efficacy of LBPs for the prevention of atopic disease are constrained by the necessity to evaluate early measures of efficacy, and age one year is thus a desirable end point. The clinical relevance of these one year allergic phenotypes is emphasized by the fact that infants with a positive allergic composite index (defined as having two or more atopic outcomes (AD, FS, RW or AW) at age one year), were 2.14 times more likely than healthy controls to have a positive allergic composite index at age five years (defined as having two or more diagnoses of asthma, allergic rhinitis, atopic dermatitis, and food sensitization); 3.15 times more likely to have asthma; 2.28 times more likely to have allergic rhinitis; 8.08 times more likely to have atopic dermatitis; and 10.64 times more likely to have food sensitization at age five years (Figure IB).

[00293] Bacterial genera identified by at least one machine learning method to be consistently reduced in relative abundance among cases relative to controls with an area under the curve >0.6 and a prevalence of at least 15% in controls were included in the final nomination. Using these methods, nine bacterial genera were identified whose relative abundances were inversely related to the risk of developing at least two allergic disease manifestations at age one year (Table 3).

*=known butyrate producer †=known acetate producer 0=known propionate producer

[00294] No bacterial genera were identified to be consistently increased in cases relative to controls, supporting the hypothesis that supplementation with ‘missing microbes’ in early life may reduce an infant’s risk of developing allergic disease in childhood.

[00295] Data from subjects with atopy+wheeze suggest that infants with 2 or more atopic disease indications at 1 year of age lack certain gut bacteria. Subjects with multiple atopic disease indications at 1 year of age are significant, because data from Figure IB support the hypothesis that children with a positive atopic composite score at 1 year of age (i.e., two or more atopic indications at 1 year of age) are at increased risk of exhibiting two or more allergic diseases at age 5 years of age.

[00296] Although it is now well established that gut microbiota communities of infants who go on to develop allergic manifestations differ from those of healthy children (See Boutin 2016), few clinical trials have been completed in an attempt to translate these findings to clinical practice. Moreover, many of the small clinical trials completed to date have shown disappointing results ( See Stephanie Tan- Lim CC and Ann Esteban-Ipac NR. World Allergy Organ J. 11:1-13 (2018) and Cabana MD, et al. Pediatrics 142:S213.1-S213 (2018)), likely at least in part because many live-bacterial probiotics used in these trials have focused on only one or a few microbes with little population-based evidence to support their use in allergic disease. Many of the functional features of the gut microbiota associated with protection against allergy, such as the production of short-chain fatty acid (SCFA) metabolites, depend on the existence of a complex, dynamic community of microbes. Thus, supplementation with a microbial consortium may be a more effective strategy for modulating the development of allergic disease (See Stein RR, et al. Elife. 7:1-17 (2018) and Gilbert JA, et al. Nature 535:94-103 (2016)). Based on our results, a nine- component microbial cocktail is nominated comprised of bacteria from the following genera for use in a clinical trial as an LBP for the primary prevention of allergic disease: Faecalibacterium, Lachnospira, Coprococcus

( Anaerostipes/Eubacterium E ), Oscillospira ( Intestinimonas/Flavonifractor ), Roseburia, Blautia, Dorea, Parabacteroides, and Ruminococcus ( See Tables 1-3). Alternatively, a nine-component microbial cocktail is nominated comprised of bacteria from the following genera for use in a clinical trial as an LBP for the primary prevention of allergic disease: Faecalibacterium, Lachnospira, Coprococcus ( Anaerostipes/Eubacterium E ), Oscillospira ( Intestinimonas/Flavonifractor ), Roseburia, Blautia, Tyzzerella, Parabacteroides, and Ruminococcus. Future work would also be appropriate to determine the safety and efficacy of an LBP in both mice and in humans.

[00297] Seven of the nine nominated bacterial genera belong to the class Clostridia, six are known producers of SCFAs (Tables 3-4), and none are known pathogens or pathobionts. Table 4 presents additional information on SCFAs produced by the different nominated bacterial genera. [00298] Short-chain fatty acid-producing capacity of bacterial genera nominated for inclusion in a live biotherapeutic product designed for allergic disease prevention and references indicating a potentially therapeutic immunomodulatory effect of each genus.

N/A: Indicates short-chain fatty acid production by this bacterial genus has not been reported.

[00299] When placed within the context of current literature describing the beneficial immunomodulatory effects of certain gut microbiota bacteria in early life, these results suggest that supplementation with a bacterial composition (i.e., an LBP) comprised of multiple bacterial genera in infancy may prevent the onset or progression of a wide array of allergic disease manifestations. Supplementation with an LBP may also be able to treat allergic diseases. Future work will determine whether administration of the proposed bacterial composition in infancy is safe and can protect against the onset and/or reduce the severity of allergic disease manifestations in mice and humans. Therefore, the present findings may be useful in guiding the development of future rigorous clinical trials.

Example 4. Additional nomination for clinical measurements

[00300] The microbiome data were also examined at both sOTU (strain level) and also at aggregated genus level.

[00301] Demultiplexed fastq-files were processed to generate sub- Operational Taxonomic Units (sOTUs) as recommended by the deblur workflow (Amir, 2017) (www.github.com/biocore/deblur). The taxonomic assignment of the sOTUs was performed using the Greengenes database (version 13_8) (www.greengenes.secondgenome.com/downloads/database/13_8). All microbiome data analyses were performed in the statistical software package R version 3.3.0, using packages including phyloseq (McMurdie and Holmes, 2013) (www.github.com/joey711/phyloseq), randomForest (Breiman, 2001) (www.stat.berkeley.edu/~breiman/RandomForests/), and mixOmicsCaret (www.github.com/jonathanth/mixOmicsCaret). The overall data analysis workflow is described in Figure 5. The Data QC step defines the healthy cohort for all clinical measurements, removes rare sOTUs and low-quality reads. The microbiome data is examined at both sOTU (strain level) and also at aggregated genus level. In order to correct for sequencing variation across the samples and sequencing batch effects, the microbiome data was rarefied and percentile normalized, respectively. Additionally, for some methods which can incorporate sequencing depth and batch effects as parameters in the modeling, raw microbiome data was used along with sequencing batch and depth information as additional parameters.

[00302] Four distinct differential abundance methods were used to nominate taxa that are significantly and differentially abundant between a clinical measurement and healthy individuals. All tests were repeated at two taxonomic levels (genus and sOTUs), as summarized in Figure 5. Differences in the relative abundances at the genus and sOTU levels were analyzed using Wilcoxon rank-sum tests, and a number of differential abundance tests present in the R package DATest (Russel et ah, 2018) (https://github.com/Russel88/DAtest) including t-test, Wilcoxon rank-sum test, linear regressions, limma, SAMseq, edgeR, DESeq2, metagenomeSeq, and ANCOM. The importance of taxa (at genus and sOTU levels) were also determined using the sparse Partial Ueast Square - Determinant Analysis (sPUS-DA) method (Chung and Keles, 2010) and the random forest classification methods. An optimum number of input variables were selected using repeated 10-fold cross- validation of the Area Under the Curve (AUC) statistic to avoid overfitting.

[00303] Data quality control (QC) was also performed as shown in Figure 6 to ensure definition of the healthy cohort.

[00304] The taxa were also filtered for prevalence greater than 15% in the healthy children (Figure 7) and their relative abundances greater than 0.2% (Figure 8) in healthy populations. A significance level of 0.05 was used in all analyses. An AUC cutoff of greater than 0.6 was also used in all analyses.

[00305] Representative strain sequences obtained via these methods using the Greengenes database include SEQ ID NOs: 1-26.

[00306] Using these methods, the microbiome data collected at 3 months was used to nominate taxa that are protective for clinical measurements measured at 1 year. The clinical measurements for which the method was applied include: atopic dermatitis, food sensitization, recurrent wheeze, and atopy and wheeze. The nomination for each clinical measurement individually is listed in Table 5 below. These genera were nominated based on the combined results from modeling methods as described above. A summary of results is shown in Figure 9.

[00307] The nominated genera for atopic dermatitis at 1 year include Faecalibacterium, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, and Ruminococcus. In some embodiments, Tyzzerella may be substituted for Dorea.

[00308] The nominated genera for food sensitization at 1 year include Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, and Ruminococcus. In some embodiments, Tyzzerella may be substituted for Dorea.

[00309] The nominated genera for recurrent wheeze at 1 year include Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, and Blautia. In some embodiments, Tyzzerella may be substituted for Dorea.

[00310] The nominated genera for atopy and wheeze at 1 year include Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, and Ruminococcus. In some embodiments, Tyzzerella may be substituted for Dorea.

[00311] There is a significant overlap in the nominated genera for the individual clinical measurements. These genera can be combined into a single nomination for a composite atopic disease which is defined as having any one of the clinical measurements: atopic dermatitis, food sensitization, recurrent wheeze, and atopy and wheeze. The nominated genera for the atopic disease (i.e., atopic composite disease) include Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, and Ruminococcus. In some embodiments, Tyzzerella may be substituted for Dorea. Table 5. Nominated genera for clinical measurements atopic dermatitis, food sensitization, recurrent wheeze, and atopy and wheeze (all diagnosed at one year after birth). The tick mark indicates a genus nominated in a clinical measurement

[00312] The sequences of the nominated genera were also mapped to the Genomic Taxonomy Database (version 86) (www.gtdb.ecogenomic.org/), and their corresponding genera are listed in Table 6 below.

Table 6. Nominated genera correspondence across two taxonomic classification methods

[00313] This additional analysis supports those nominations described in Example 3, and also comprise some nominations not described in Example 3. For example, Blautia is included in the genus nominated for recurrent wheeze, and Oscillospira (Intestinimonas/Flavonifractor) is included in the genus nominated for atopy and wheeze.

EXEMPLARY EMBODIMENTS 1. A method of treating one or more of an atopic disease in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus.

2. The method of embodiment 1, wherein the method comprises administering one or more bacteria of the genus Lachnospira.

3. The method of embodiment 2, wherein the one or more bacteria of genus Lachnospira are chosen from Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, and Lachnospira rogosae.

4. The method of embodiment 3, wherein the one or more bacteria of genus Lachnospira is Lachnospira eligens.

5. The method of embodiment 2, wherein the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7.

6. The method of embodiment 2, wherein 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

7. The method of any one of embodiments 1-6, wherein the method comprises administering one or more bacteria of the genus Faecalibacterium.

8. The method of embodiment 7, wherein the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii.

9. The method of embodiment 7, wherein the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3.

10. The method of embodiment 7, wherein the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

11. The method of any one of embodiments 1-10, wherein the method comprises administering one or more bacteria of the genus Roseburia.

12. The method of embodiment 11, wherein the one or more bacteria of genus Roseburia is Roseburia hominis. 13. The method of embodiment 11, wherein the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14.

14. The method of embodiment 11, wherein the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

15. The method of any one of embodiments 1-14, wherein the method comprises administering one or more bacteria of the genus Blautia.

16. The method of embodiment 15, wherein the one or more bacteria of genus Blautia is Blautia hydrogenotrophica.

17. The method of embodiment 15, wherein the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22.

18. The method of embodiment 15, wherein the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

19. The method of any one of embodiments 1-18, wherein the method comprises administering one or more bacteria of the genus Parabacteroides.

20. The method of embodiment 19, wherein the one or more bacteria of genus Parabacteroides is Parabacteroides distasonis.

21. The method of embodiment 19, wherein the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises SEQ ID NO: 23.

22. The method of embodiment 19, wherein the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23.

23. The method of any one of embodiments 1-22, wherein the method comprises administering one or more bacteria of the genus Oscillospira.

24. The method of embodiment 23, wherein the one or more bacteria of genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii.

25. The method of embodiment 23, wherein the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12. 26. The method of embodiment 23, wherein the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

27. The method of any one of embodiments 1-26, wherein the method comprises administering one or more bacteria of the genus Dorea.

28. The method of embodiment 27, wherein the 16s rRNA gene of the one or more bacteria of genus Dorea comprises SEQ ID NO: 26.

29. The method of embodiment 27, wherein the 16s rRNA gene of the one or more bacteria of genus Dorea comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26.

30. The method of any one of embodiments 1-29, wherein the method comprises administering one or more bacteria of the genus Ruminococcus.

31. The method of embodiment 30, wherein the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15-19 or 24-25.

32. The method of embodiment 30, wherein the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

33. The method of any one of embodiments 1-32, wherein the method comprises administering one or more bacteria of the genus Coprococcus.

34. The method of embodiment 33, wherein the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10.

35. The method of embodiment 33, wherein the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

36. The method of any one of embodiment 1-35, wherein the atopic disease comprises asthma, food allergy, food sensitization, recurrent wheeze, allergic rhinitis, eczema, and/or atopic dermatitis.

37. A method of treating atopic dermatitis in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus .

38. The method of embodiment 37, wherein the method comprises administering one or more bacteria of the genus Faecalibacterium.

39. The method of embodiment 38, wherein the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii.

40. The method of embodiment 38, wherein the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3.

41. The method of embodiment 38, wherein the 16s rRNA gene ofthe one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

42. The method of any one of embodiments 37-41, wherein the method comprises administering one or more bacteria of the genus Oscillospira.

43. The method of embodiment 42, wherein the one or more bacteria of genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii.

44. The method of embodiment 42, wherein the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12.

45. The method of embodiment 42, wherein the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

46. The method of any one of embodiment 37-45, wherein the method comprises administering one or more bacteria of the genus Roseburia.

47. The method of embodiment 46, wherein the one or more bacteria of genus Roseburia is Roseburia hominis.

48. The method of embodiment 46, wherein the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14.

49. The method of embodiment 46, wherein the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14. 50. The method of any one of embodiment 37-49, wherein the method comprises administering one or more bacteria of the genus Blautia.

51. The method of embodiment 50, wherein the one or more bacteria of genus Blautia is Blautia hydrogenotrophica.

52. The method of embodiment 50, wherein the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22.

53. The method of embodiment 50, wherein the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

54. The method of any one of embodiments 37-53, wherein the method comprises administering one or more bacteria of the genus Parabacteroides.

55. The method of embodiment 54, wherein the one or more bacteria of genus Parabacteroides is Parabacteroides distasonis.

56. The method of embodiment 54, wherein the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises SEQ ID NO: 23.

57. The method of embodiment 54, wherein the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23.

58. The method of any one of embodiments 37-57, wherein the method comprises administering one or more bacteria of the genus Dorea.

59. The method of embodiment 58, wherein the 16s rRNA gene of the one or more bacteria of genus Dorea comprises SEQ ID NO: 26.

60. The method of embodiment 58, wherein the 16s rRNA gene of the one or more bacteria of genus Dorea comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26.

61. The method of any one of embodiments 37-60, wherein the method comprises administering one or more bacteria of the genus Ruminococcus.

62. The method of embodiment 61, wherein the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15-19 or 24-25. 63. The method of embodiment 61, wherein the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

64. The method of any one of embodiments 37-63, wherein the method comprises administering one or more bacteria of the genus Coprococcus.

65. The method of embodiment 64, wherein the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10.

66. The method of embodiment 64, wherein the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

67. A method of treating food sensitization and/or food allergy in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, or Ruminococcus.

68. The method of embodiment 67, wherein the method comprises administering one or more bacteria of the genus Faecalibacterium.

69. The method of embodiment 68, wherein the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii.

70. The method of embodiment 68, wherein the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3.

71. The method of embodiment 68, wherein the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

72. The method of any one of embodiments 67-71, wherein the method comprises administering one or more bacteria of the genus Lachnospira.

73. The method of embodiment 72, wherein the one or more bacteria of genus Lachnospira are chosen from Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, and Lachnospira rogosae. 74. The method of embodiment 73, wherein the one or more bacteria of genus Lachnospira is Lachnospira eligens.

75. The method of embodiment 72, wherein the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7.

76. The method of embodiment 72, wherein 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

77. The method of any one of embodiment 67-76, wherein the method comprises administering one or more bacteria of the genus Oscillospira.

78. The method of embodiment 77, wherein the one or more bacteria of genus Oscillospira are chosen from Intestinimonas hutyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii.

79. The method of embodiment 77, wherein the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12.

80. The method of embodiment 77, wherein the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

81. The method of any one of embodiments 67-80, wherein the method comprises administering one or more bacteria of the genus Rosehuria.

82. The method of embodiment 81, wherein the one or more bacteria of genus Rosehuria is Rosehuria hominis.

83. The method of embodiment 81, wherein the 16s rRNA gene ofthe one or more bacteria of genus Rosehuria comprises SEQ ID NOs: 13-14.

84. The method of embodiment 81, wherein the 16s rRNA gene of the one or more bacteria of genus Rosehuria comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

85. The method of any one of embodiments 67-84, wherein the method comprises administering one or more bacteria of the genus Blautia.

86. The method of embodiment 85, wherein the one or more bacteria of the genus Blautia is Blautia hydrogenotrophica. 87. The method of embodiment 85, wherein the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22.

88. The method of embodiment 85, wherein the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

89. The method of any one of embodiments 67-88, wherein the method comprises administering one or more bacteria of the genus Dorea.

90. The method of embodiment 89, wherein the 16s rRNA gene of the one or more bacteria of genus Dorea comprises SEQ ID NO: 26.

91. The method of embodiment 89, wherein the 16s rRNA gene of the one or more bacteria of genus Dorea comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26.

92. The method of any one of embodiments 67-91, wherein the method comprises administering one or more bacteria of the genus Ruminococcus.

93. The method of embodiment 92, wherein the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15-19 or 24-25.

94. The method of embodiment 92, wherein the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

95. The method of any one of embodiments 67-94, wherein the method comprises administering one or more bacteria of the genus Coprococcus.

96. The method of embodiment 95, wherein the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10.

97. The method of embodiment 95, wherein the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

98. A method of treating recurrent wheeze in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, or Blautia. 99. A method of treating recurrent wheeze in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, or Roseburia.

100. The method of embodiment 98 or 99, wherein the method comprises administering one or more bacteria of the genus Faecalibacterium.

101. The method of embodiment 100, wherein the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii.

102. The method of embodiment 100, wherein the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3.

103. The method of embodiment 100, wherein the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

104. The method of any one of embodiments 98-103, wherein the method comprises administering one or more bacteria of the genus Lachnospira.

105. The method of embodiment 104, wherein the one or more bacteria of genus Lachnospira are chosen from Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, and Lachnospira rogosae.

106. The method of embodiment 105, wherein the one or more bacteria of genus Lachnospira is Lachnospira eligens.

107. The method of embodiment 104, wherein the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7.

108. The method of embodiment 104, wherein 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

109. The method of any one of embodiments 98-108, wherein the method comprises administering one or more bacteria of the genus Oscillospira.

110. The method of embodiment 109, wherein the one or more bacteria of genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii. 111. The method of embodiment 109, wherein the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12.

112. The method of embodiment 109, wherein the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

113. The method of any one of embodiments 98-112, wherein the method comprises administering one or more bacteria of the genus Roseburia.

114. The method of embodiment 113, wherein the one or more bacteria of genus Roseburia is Roseburia hominis.

115. The method of embodiment 113, wherein the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14.

116. The method of embodiment 113, wherein the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

117. The method of any one of embodiments 98-116, wherein the method comprises administering one or more bacteria of the genus Coprococcus.

118. The method of embodiment 117, wherein the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10.

119. The method of embodiment 117, wherein the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

120. The method of any one of embodiments 98 or 100-120, wherein the method comprises administering one or more bacteria of the genus Blautia.

121. The method of embodiment 120, wherein the one or more bacteria of genus Blautia is Blautia hydrogenotrophica.

122. The method of embodiment 120, wherein the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22.

123. The method of embodiment 120, wherein the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22. 124. A method of treating atopy and wheeze in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, or Ruminococcus.

125. A method of treating atopy and wheeze in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Roseburia, Blautia, Parabacteroides, or Ruminococcus.

126. The method of embodiment 124 or embodiment 125, wherein the method comprises administering one or more bacteria of the genus Faecalibacterium.

127. The method of embodiment 126, wherein the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii.

128. The method of embodiment 126, wherein the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3.

129. The method of embodiment 126, wherein the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

130. The method of any one of embodiments 124-129, wherein the method comprises administering one or more bacteria of the genus Lachnospira.

131. The method of embodiment 130, wherein the one or more bacteria of genus Lachnospira are chosen from Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, and Lachnospira rogosae.

132. The method of embodiment 131, wherein the one or more bacteria of genus Lachnospira is Lachnospira eligens.

133. The method of embodiment 130, wherein the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7.

134. The method of embodiment 130, wherein 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7. 135. The method of any one of embodiments 124-134, wherein the method comprises administering one or more bacteria of the genus Roseburia.

136. The method of embodiment 135, wherein the one or more bacteria of genus Roseburia is Roseburia hominis.

137. The method of embodiment 135, wherein the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14.

138. The method of embodiment 135, wherein the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

139. The method of any one of embodiments 124-138, wherein the method comprises administering one or more bacteria of the genus Blautia.

140. The method of embodiment 139, wherein the one or more bacteria of genus Blautia is Blautia hydrogenotrophica.

141. The method of embodiment 139, wherein the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22.

142. The method of embodiment 139, wherein the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

143. The method of any one of embodiments 124-142, wherein the method comprises administering one or more bacteria of the genus Parabacteroides.

144. The method of embodiment 143, wherein the one or more bacteria of genus Parabacteroides is Parabacteroides distasonis.

145. The method of embodiment 143, wherein the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises SEQ ID NO: 23.

146. The method of embodiment 143, wherein the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23.

147. The method of any one of embodiments 124-146, wherein the method comprises administering one or more bacteria of the genus Ruminococcus. 148. The method of embodiment 147, wherein the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15-19 or 24-25.

149. The method of embodiment 147, wherein the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

150. The method of any one of embodiments 124-149, wherein the method comprises administering one or more bacteria of the genus Coprococcus.

151. The method of embodiment 150, wherein the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10.

152. The method of embodiment 150, wherein the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

153. The method of any one of embodiments 124 or 126-152, wherein the method comprises administering one or more bacteria of genus Oscillospira.

154. The method of embodiment 153, wherein the one or more bacteria of the genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii.

155. The method of embodiment 153, wherein the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12.

156. The method of embodiment 153, wherein the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

157. The method of any one of embodiments 1-156, wherein the atopic disease comprises asthma, food allergy, food sensitization, recurrent wheeze, allergic rhinitis, eczema, and/or atopic dermatitis.

158. The method of any one of embodiments 1-157, wherein the bacterial composition comprises bacteria of two of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, or Ruminococcus.

159. The method of any one of embodiments 1-158, wherein the bacterial composition comprises bacteria of three of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, or Ruminococcus.

160. The method of any one of embodiments 1-159, wherein the bacterial composition comprises bacteria of four of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, or Ruminococcus.

161. The method of any one of embodiments 1-160, wherein the bacterial composition comprises bacteria of five, six, seven, eight, or nine of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, or Ruminococcus.

162. A method of treating one or more of an atopic disease in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, and Ruminococcus.

163. A method of treating atopic dermatitis in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, and Ruminococcus.

164. A method of treating food sensitization and/or food allergy in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, and Ruminococcus.

165. A method of treating recurrent wheeze in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, and Blautia.

166. A method of treating atopy and wheeze in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, and Ruminococcus. 167. A method of treating one or more of an atopic disease in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea,

Parabacteroides, or Ruminococcus.

168. A method of treating one or more of an atopic disease in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Anaerostipes, Eubacterium E, Instestinimonas, Flavonifractor, Roseburia, Ruminococcus B, Ruminococcus _E, Blautia, Blautia A, Tyzzerella, or Parabacteroides.

169. A method of treating one or more of an atopic disease in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera that produce short- chain fatty acids.

170. The method of embodiment 169, wherein the short-chain fatty acids are chosen from butyrate, acetate, and propionate.

171. The method of any one of embodiments 1-170, wherein the subject is a human infant or a pregnant female.

172. The method of embodiment 171, wherein the human infant is one year old or younger.

173. The method of embodiment 172, wherein the human infant is three months old or younger, 6 months old or younger, or 9 months old or younger.

174. The method of any one of embodiments 1-173, wherein the bacterial composition is administered prophylactically.

175. The method of any one of embodiments 1-174, wherein the bacterial composition is administered orally or rectally.

176. The method of any one of embodiments 1-175, wherein the bacterial composition is administered topically.

177. The method of any one of embodiments 1-176 wherein the bacterial composition is formulated as a liquid suspension. 178. The method of any one of embodiments 1-177, wherein the administering results in an increase in the population of at least one bacteria of the genera comprised in the bacterial composition.

179. The method of embodiment 178, wherein the increase is determined using quantitative polymerase chain reaction.

180. The method of embodiment 179, wherein the increase is monitored by the detection of a metabolite present in a sample from said subject.

181. A bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus , in combination with a carrier.

182. The bacterial composition of embodiment 181, wherein the bacterial composition comprises one or more bacteria of the genus Faecalibacterium.

183. The bacterial composition of embodiment 182, wherein the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii.

184. The bacterial composition of embodiment 182, wherein the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3.

185. The bacterial composition of embodiment 182, wherein the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

186. The bacterial composition of any one of embodiments 181-185, wherein the bacterial composition comprises one or more bacteria of the genus Lachnospira.

187. The bacterial composition of embodiment 186, wherein the one or more bacteria of genus Lachnospira are chosen from Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, and Lachnospira rogosae.

188. The bacterial composition of embodiment 187, wherein the one or more bacteria of genus Lachnospira is Lachnospira eligens.

189. The bacterial composition of embodiment 186, wherein the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7. 190. The bacterial composition of embodiment 186, wherein 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

191. The bacterial composition of any one of embodiments 181-190, wherein the bacterial composition comprises one or more bacteria of the genus Oscillospira.

192. The bacterial composition of embodiment 191, wherein the one or more bacteria of genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii.

193. The bacterial composition of embodiment 191, wherein the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12.

194. The bacterial composition of embodiment 191, wherein the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

195. The bacterial composition of any one of embodiments 181-194, wherein the bacterial composition comprises one or more bacteria of the genus Roseburia.

196. The bacterial composition of embodiment 195, wherein the one or more bacteria of genus Roseburia is Roseburia hominis.

197. The bacterial composition of embodiment 195, wherein the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14.

198. The bacterial composition of embodiment 195, wherein the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

199. The bacterial composition of any one of embodiments 181-198, wherein the bacterial composition comprises one or more bacteria of the genus Blautia.

200. The bacterial composition of embodiment 199, wherein the one or more bacteria of genus Blautia is Blautia hydrogenotrophica .

201. The bacterial composition of embodiment 199, wherein the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22. 202. The bacterial composition of embodiment 199, wherein the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

203. The bacterial composition of any one of embodiments 181-202, wherein the bacterial composition comprises one or more bacteria of the genus Parabacteroides.

204. The bacterial composition of embodiment 203, wherein the one or more bacteria of genus Parabacteroides is Parabacteroides distasonis.

205. The bacterial composition of embodiment 203, wherein the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises SEQ ID NO: 23.

206. The bacterial composition of embodiment 203, wherein the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23.

207. The bacterial composition of any one of embodiments 181-206, wherein the bacterial composition comprises one or more bacteria of the genus Dorea.

208. The bacterial composition of embodiment 207, wherein the 16s rRNA gene of the one or more bacteria of genus Dorea comprises SEQ ID NO: 26.

209. The bacterial composition of embodiment 207, wherein the 16s rRNA gene of the one or more bacteria of genus Dorea comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26.

210. The bacterial composition of any one of embodiments 181-209, wherein the bacterial composition comprises one or more bacteria of the genus Ruminococcus.

211. The bacterial composition of embodiment 210, wherein the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15-19 or 24-25.

212. The bacterial composition of embodiment 210, wherein the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

213. The bacterial composition of any one of embodiments 181-212, wherein the bacterial composition comprises one or more bacteria of the genus Coprococcus. 214. The bacterial composition of embodiment 213, wherein the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10.

215. The bacterial composition of embodiment 213, wherein the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

216. The bacterial composition of any one of embodiments 181-215, wherein the bacteria are present in an amount effective for treating atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze, in a subject in need thereof.

217. The bacterial composition of any one of embodiments 181-216, for use in treating atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze, in a subject in need thereof.

218. The bacterial composition of any one of embodiments 181-217, wherein the composition comprises bacteria of three, four, five, six, seven, eight, or nine of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus.

219. The bacterial composition of any one of embodiments 181-218, wherein the bacteria are substantially pure.

220. A method of determining the likelihood of development of atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze in a subject, comprising determining the levels of bacteria of two or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus in a sample from said subject, and comparing said levels to a reference or a healthy subject, wherein a decrease in the levels of the bacteria indicates the increased likelihood of development of atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze.

221. The method of embodiment 220, comprising determining the levels of one or more bacteria of the genus Faecalibacterium.

222. The method of embodiment 221, wherein the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii. 223. The method of embodiment 221, wherein the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3.

224. The method of embodiment 221, wherein the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

225. The method of any one of embodiments 220-224, comprising determining the levels of one or more bacteria of the genus Lachnospira.

226. The method of embodiment 225, wherein the one or more bacteria of genus Lachnospira are Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, or Lachnospira rogosae.

227. The method of any embodiment 226, wherein the one or more bacteria of genus Lachnospira is Lachnospira eligens.

228. The method of embodiment 225, wherein the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7.

229. The method of embodiment 225, wherein 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

230. The method of any one of embodiments 220-229, comprising determining the levels of one or more bacteria of the genus Oscillospira.

231. The method of embodiment 230, wherein the one or more bacteria of genus Oscillospira are chosen from Intestinimonas butyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii.

232. The method of embodiment 230, wherein the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12.

233. The method of embodiment 230, wherein the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

234. The method of any one of embodiments 220-233, comprising determining the levels of one or more bacteria of the genus Roseburia. 235. The method of embodiment 234, wherein the one or more bacteria of genus Roseburia is Roseburia hominis.

236. The method of embodiment 234, wherein the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14.

237. The method of embodiment 234, wherein the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

238. The method of any one of embodiments 220-237, comprising determining the levels of one or more bacteria of the genus Blautia.

239. The method of embodiment 238, wherein the one or more bacteria of genus Blautia is Blautia hydrogenotrophica.

240. The method of embodiment 238, wherein the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22.

241. The method of embodiment 238, wherein the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

242. The method of any one of embodiments 220-241, comprising determining the levels of one or more bacteria of the genus Parabacteroides.

243. The method of embodiment 242, wherein the one or more bacteria of genus Parabacteroides is Parabacteroides distasonis.

244. The method of embodiment 242, wherein the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises SEQ ID NO: 23.

245. The method of embodiment 242, wherein the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23.

246. The method of any one of embodiments 220-245, comprising determining the levels of one or more bacteria of the genus Dorea.

247. The method of embodiment 246, wherein the 16s rRNA gene of the one or more bacteria of genus Dorea comprises SEQ ID NO: 26. 248. The method of embodiment 246, wherein the 16s rRNA gene of the one or more bacteria of genus Dorea comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26.

249. The method of any one of embodiments 220-248, comprising determining the levels of one or more bacteria of the genus Ruminococcus .

250. The method of embodiment 249, wherein the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15-19 or 24-25.

251. The method of embodiment 249, wherein the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

252. The method of any one of embodiments 220-251, comprising determining the levels of one or more bacteria of the genus Coprococcus.

253. The method of embodiment 252, wherein the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10.

254. The method of embodiment 252, wherein the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 8-10.

255. The method of any one of embodiments 220-254, further comprising determining the levels of a metabolite present in a sample from said subject.

256. The method of any one of embodiments 220-255, further comprising administering an effective amount of the composition of any one of embodiments 181-219 to a subject determined to have an increased likelihood of development of atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze.

257. A method of treating one or more of an atopic disease in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, or Ruminococcus.

258. The method of embodiment 257, wherein the method comprises administering one or more bacteria of the genus Tyzzerella. 259. A method of treating atopic dermatitis in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, or Ruminococcus .

260. The method of embodiment 259, wherein the method comprises administering one or more bacteria of the genus Tyzzerella.

261. A method of treating food sensitization and/or food allergy in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, or Ruminococcus.

262. The method of embodiment 261, wherein the method comprises administering one or more bacteria of the genus Tyzzerella.

263. A method of treating one or more of an atopic disease in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, and Ruminococcus.

264. A method of treating atopic dermatitis in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, and Ruminococcus.

265. A method of treating food sensitization and/or food allergy in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, and Ruminococcus.

266. A method of treating one or more of an atopic disease in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, or Ruminococcus. 267. A bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, or Ruminococcus, in combination with a carrier.

268. The bacterial composition of embodiment 267, wherein the bacterial composition comprises one or more bacteria of the genus Tyzzerella.

269. The bacterial composition of any one of embodiments 267-268, wherein the composition comprises bacteria of three, four, five, six, seven, eight, or nine of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, or Ruminococcus.

270. A method of determining the likelihood of development of atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze in a subject, comprising determining the levels of bacteria of two or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Tyzzerella, Parabacteroides, or Ruminococcus in a sample from said subject, and comparing said levels to a reference or a healthy subject, wherein a decrease in the levels of the bacteria indicates the increased likelihood of development of atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze.

271. The method of embodiment 270, comprising determining the levels of one or more bacteria of the genus Tyzzerella.

EQUIVALENTS

[00314] The foregoing written specification is considered to be sufficient to enable one skilled in the art to practice the embodiments. The foregoing description and Examples detail certain embodiments and describes the best mode contemplated by the inventors. It will be appreciated, however, that no matter how detailed the foregoing may appear in text, the embodiment may be practiced in many ways and should be construed in accordance with the appended claims and any equivalents thereof.

[00315] As used herein, the term about refers to a numeric value, including, for example, whole numbers, fractions, and percentages, whether or not explicitly indicated. The term about generally refers to a range of numerical values (e.g., +/-5-10% of the recited range) that one of ordinary skill in the art would consider equivalent to the recited value (e.g., having the same function or result). When terms such as at least and about precede a list of numerical values or ranges, the terms modify all of the values or ranges provided in the list. In some instances, the term about may include numerical values that are rounded to the nearest significant figure.

Claims

What is Claimed is:

1. A method of treating one or more of an atopic disease in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, or Parabacteroides .

2. The method of claim 1, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera: a. Faecalibacterium, Lachnospira, Coprococcus, Oscillospira,

Roseburia, Blautia, Dorea, or Parabacteroides, b. Faecalibacterium, Lachnospira, Coprococcus, Oscillospira,

Roseburia, Blautia, or Parabacteroides, or c. Anaerostipes, Eubacterium E, Instestinimonas, Flavonifractor, Ruminococcus _B, Ruminococcus _E, Blautia, or Blautia_ A.

3. The method of claim 1 or 2, wherein the atopic disease comprises asthma, food allergy, food sensitization, recurrent wheeze, allergic rhinitis, eczema, and/or atopic dermatitis.

4. The method of claim 1, wherein: a. the atopic disease comprises atopic dermatitis and the bacterial composition comprises bacteria of three or more of the genera Faecalibacterium, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus, b. the atopic disease comprises atopic dermatitis and the bacterial composition comprises bacteria of three or more of the genera Faecalibacterium, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, or Ruminococcus, c. the atopic disease comprises food sensitization and/or food allergy and the bacterial composition comprises bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, or Ruminococcus, d. the atopic disease comprises food sensitization and/or food allergy and the bacterial composition comprises bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, or Ruminococcus, e. the atopic disease comprises recurrent wheeze and the bacterial composition comprises bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, or Blautia ; f. the atopic disease comprises recurrent wheeze and the bacterial composition comprises bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, or Roseburia ; g. the atopic disease comprises atopy and wheeze and the bacterial composition comprises bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, or Ruminococcus, or h. the atopic disease comprises atopy and wheeze and the bacterial composition comprises bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Roseburia, Blautia, Parabacteroides, or Ruminococcus.

5. The method of any one of claims 1 to 4, wherein the bacterial composition comprises bacteria of five, six, seven, eight, nine or ten of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, and Ruminococcus .

6. The method of claim 5, wherein: a. the atopic disease comprises atopic dermatitis and the bacterial composition comprises bacteria of the genera Faecalibacterium, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, and Ruminococcus ; b. the atopic disease comprises atopic dermatitis and the bacterial composition comprises bacteria of the genera Faecalibacterium, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, and Ruminococcus ; c. the atopic disease comprises food sensitization and/or food allergy and the bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, and Ruminococcus ; d. the atopic disease comprises food sensitization and/or food allergy and the bacterial composition comprising bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, , and Ruminococcus, e. the atopic disease comprises recurrent wheeze and the bacterial composition comprises bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, and Blautia ; or f. the atopic disease comprises atopy and wheeze and thee bacterial composition compriss bacteria of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Parabacteroides, and Ruminococcus.

7. The method of any one of claims 1 to 6 wherein: a. the method comprises administering one or more bacteria of the genus Faecalibacterium ; b. the method comprises administering one or more bacteria of the genus Faecalibacterium wherein the one or more bacteria of genus Faecalibacterium is Faecalibacterium prausnitzii c. the method comprises administering one or more bacteria of the genus Faecalibacterium wherein the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises SEQ ID NOs: 1-3; or d. the method comprises administering one or more bacteria of the genus Faecalibacterium wherein the 16s rRNA gene of the one or more bacteria of genus Faecalibacterium comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 1-3.

8. The method of any one of claims 1 to 7 wherein: a. the method comprises administering one or more bacteria of the genus Lachnospira ; b. the method comprises administering one or more bacteria of the genus Lachnospira and wherein the one or more bacteria of genus Lachnospira are chosen from Lachnospira eligens, Lachnospira pectinoschiza, Lachnospira multipara, and Lachnospira rogosae c. the method comprises administering one or more bacteria of the genus Lachnospira and wherein the one or more bacteria of genus Lachnospira is Lachnospira pectinoschiza, Lachnospira multipara, and Lachnospira rogosae; d. the method comprises administering one or more bacteria of the genus Lachnospira and wherein the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises SEQ ID NOs: 4-7; or e. the method comprises administering one or more bacteria of the genus Lachnospira and wherein the 16s rRNA gene of the one or more bacteria of genus Lachnospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 4-7.

9. The method of any one of claims 1 to 8 wherein: a. the method comprises administering one or more bacteria of the genus Coprococcus; b. the method comprises administering one or more bacteria of the genus Coprococcus and wherein the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises SEQ ID NOs: 8-10; c. the method comprises administering one or more bacteria of the genus Coprococcus and wherein the 16s rRNA gene of the one or more bacteria of genus Coprococcus comprises a sequence that is at least 95%, 96%, 97%,

98%, or 99% identical to SEQ ID NOs: 8-10.

10. The method of any one of claims 1 to 9 wherein: a. the method comprises administering one or more bacteria of the genus Oscillospira; b. the method comprises administering one or more bacteria of the genus Oscillospira and wherein the one or more bacteria of genus Oscillospira are chosen from Intestinimonas hutyriciproducens, Intestinimonas massillensis, and Flavonifractor plautii; c. the method comprises administering one or more bacteria of the genus Oscillospira and wherein the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises SEQ ID NOs: 11-12; or d. the method comprises administering one or more bacteria of the genus Oscillospira and wherein the 16s rRNA gene of the one or more bacteria of genus Oscillospira comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 11-12.

11. The method of any one of claims 1 to 10 wherein: a. the method comprises administering one or more bacteria of the genus Roseburia, b. the method comprises administering one or more bacteria of the genus Roseburia and wherein the one or more bacteria of genus Roseburia is Roseburia hominis c. the method comprises administering one or more bacteria of the genus Roseburia and wherein the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises SEQ ID NOs: 13-14; or d. the method comprises administering one or more bacteria of the genus Roseburia and wherein the 16s rRNA gene of the one or more bacteria of genus Roseburia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13-14.

12. The method of any one of claims 1 to 11 wherein: a. the method comprises administering one or more bacteria of the genus Blautia, b. the method comprises administering one or more bacteria of the genus Blautia and wherein the one or more bacteria of genus Blautia is Blautia hydrogenotrophica; c. the method comprises administering one or more bacteria of the genus Blautia and wherein the 16s rRNA gene of the one or more bacteria of genus Blautia comprises SEQ ID NOs: 20-22; or d. the method comprises administering one or more bacteria of the genus Blautia and wherein the 16s rRNA gene of the one or more bacteria of genus Blautia comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 20-22.

13. The method of any one of claims 1 to 12 wherein: a. the method comprises administering one or more bacteria of the genus Dorea; b. the method comprises administering one or more bacteria of the genus Dorea and wherein the 16s rRNA gene of the one or more bacteria of genus Dorea comprises SEQ ID NO: 26; or c. the method comprises administering one or more bacteria of the genus Dorea and wherein the 16s rRNA gene of the one or more bacteria of genus Dorea comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26.

14. The method of any one of claims 1 to 13 wherein: a. the method comprises administering one or more bacteria of the genus Parabacteroides ; b. the method comprises administering one or more bacteria of the genus Parabacteroides and wherein the one or more bacteria of genus Parabacteroides is Parabacteroides distasonis c. the method comprises administering one or more bacteria of the genus Parabacteroides and wherein the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises SEQ ID NO: 23; or d. the method comprises administering one or more bacteria of the genus Parabacteroides and wherein the 16s rRNA gene of the one or more bacteria of genus Parabacteroides comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23.

15. The method of any one of claims 1 to 14 wherein: a. the method comprises administering one or more bacteria of the genus Ruminococcus, b. the method comprises administering one or more bacteria of the genus Ruminococcus and wherein the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises SEQ ID NOs: 15-19 or 24-25; c. the method comprises administering one or more bacteria of the genus Ruminococcus and wherein the 16s rRNA gene of the one or more bacteria of genus Ruminococcus comprises a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 15-19 or 24-25.

16. A method of treating one or more of an atopic disease in a subject in need thereof, comprising administering to the subject an effective amount of a bacterial composition comprising bacteria of three or more of the genera that produce short- chain fatty acids.

17. The method of any one of claims 1-16, wherein the subject is a human infant or a pregnant female.

18. The method of any one of claims 1-17, wherein the administering results in an increase in the population of at least one bacteria of the genera comprised in the bacterial composition.

19. A bacterial composition comprising bacteria of three or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus, in combination with a carrier.

20. The bacterial composition of claim 19 for use in treating an atopic disease.

21. A method of determining the likelihood of development of atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze in a subject, comprising determining the levels of bacteria of two or more of the genera Faecalibacterium, Lachnospira, Coprococcus, Oscillospira, Roseburia, Blautia, Dorea, Parabacteroides, or Ruminococcus in a sample from said subject, and comparing said levels to a reference or a healthy subject, wherein a decrease in the levels of the bacteria indicates the increased likelihood of development of atopic dermatitis, food sensitization, food allergy, recurrent wheeze, and/or atopy and wheeze.