WO2010023178A1 - Pharmaceuticals comprising a bacterial polysaccharide - Google Patents

Pharmaceuticals comprising a bacterial polysaccharide Download PDF

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Publication number
WO2010023178A1
WO2010023178A1 PCT/EP2009/060872 EP2009060872W WO2010023178A1 WO 2010023178 A1 WO2010023178 A1 WO 2010023178A1 EP 2009060872 W EP2009060872 W EP 2009060872W WO 2010023178 A1 WO2010023178 A1 WO 2010023178A1
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Prior art keywords
polysaccharide
disease
bifidobacterium
pharmaceutical composition
group
Prior art date
Application number
PCT/EP2009/060872
Other languages
French (fr)
Inventor
Jens Kildsgaard
Thomas Janzen
Benedicte Flambard
Original Assignee
Chr. Hansen A/S
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
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Publication of WO2010023178A1 publication Critical patent/WO2010023178A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/20—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
    • A23L29/269—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of microbial origin, e.g. xanthan or dextran
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745—Bifidobacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to a bacterial polysaccharide, its use for treatment of diseases, and pharmaceutical composition comprising such a polysaccharide.
  • EPS polysaccharide
  • CPS and/or EPS polysaccharide producing lactic acid bacteria strains
  • EPS may reduce gastric mucosal inflammation in humans and have a general beneficial effect on the human immune system. This inhibition was not observed by an isogenic strain that is unable to produce EPS.
  • EPS seems to "shield-off" the cells in culture, it is contemplated that EPS are beneficial for patients suffering from a break-down in their intestinal barrier function, e.g. patients suffering from Crohns disease.
  • the data suggests that EPS might be helpful for maintaining a healthy gastrointestinal function, i.e.
  • EPS is able to influence the immune system (immune modulation), that EPS decreases or inhibit inflammatory responses (EPS has anti-inflammatory properties), and that EPS is able to maintain gut health by enhancing the intestinal mucosal barrier function.
  • immune modulation e.g. irritable bowel syndrome (IDS)
  • IDS irritable bowel syndrome
  • the CPS/EPS concept may be able to play a role during early life development
  • the present invention relates to a polysaccharide isolated from a bacterium belonging to a species of the group consisting of:
  • Bifidobacterium longum Bifidobacterium animalis, Bifidobacterium bifidum, Streptococcus thermophilus, and Lactobacillus reuteri.
  • the present invention relates to a polysaccharide isolated from the growth medium (e.g. supernatant) of a bacterium belonging to a species of the group consisting of: Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium bifidum, Streptococcus thermophilus, and Lactobacillus reuteri.
  • the growth medium may comprise milk from a mammal.
  • the bacterium belongs to a strain selected from the group consisting of: BB-12 ® free (CHCC8902), BB-12 ® (CHCC5445), ST143 (CHCC2389), RC-14 ® (CHCC5151), Bb. Longum sp. (CHCC8879), ST6008 (CHCC6008), ST9204 (CHCC9204), ST4239 (CHCC4239), BB-02 (CHCC2228), and a mutant/variant of any of these.
  • polysaccharide is an extracellular polysaccharide (EPS) or a capsular polysaccharide (CPS).
  • EPS extracellular polysaccharide
  • CPS capsular polysaccharide
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising the polysaccharide of the invention, and to a pharmaceutical composition comprising a bacterium belonging to a species of the group consisting of:
  • Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium bifidum, Streptococcus thermophilus, and Lactobacillus reuteri especially a pharmaceutical composition
  • a pharmaceutical composition comprising a bacterium belonging to a strain selected from the group consisting of: BB-12 ® free (CHCC8902), BB-12 ® (CHCC5445), ST143 (CHCC2389), RC-14 ® (CHCC5151), Bb. Longum sp. (CHCC8879), ST6008 (CHCC6008), ST9204 (CHCC9204), ST4239 (CHCC4239), BB-02 (CHCC2228), and a mutant/variant of any of these.
  • compositions which comprise living cells may further comprises a prebiotic or a growth medium, e.g. a growth medium which comprises milk from a mammal, either as a mixture or as a kit of parts, wherein the bacterial cells are packed separately from the prebiotic or growth medium.
  • a prebiotic or a growth medium e.g. a growth medium which comprises milk from a mammal, either as a mixture or as a kit of parts, wherein the bacterial cells are packed separately from the prebiotic or growth medium.
  • the present invention relates to the use of a polysaccharide of the invention, or the pharmaceutical composition of the invention, for treatment of inflammatory disease.
  • the disease is inflammatory bowel disease, colitis, or Crohn's disease.
  • the present invention relates to a method of treatment of an inflammatory disease by administering a polysaccharide or a pharmaceutical composition of the invention to the person in need of treatment.
  • the disease may be inflammatory bowel disease, colitis, or Crohn's disease.
  • mutant should be understood as a strain derived from a strain of the invention by means of e.g. genetic engineering, radiation and/or chemical treatment. It is preferred that the mutant is a functionally equivalent mutant, e.g. a mutant that has substantially the same, or improved, polysaccharide producing properties as the mother strain. Such a mutant is a part of the present invention.
  • mutant refers to a strain obtained by subjecting a strain of the invention to any conventionally used mutagenization treatment including treatment with a chemical mutagen such as ethane methane sulphonate (EMS) or N-methyl-N'-nitro-N-nitroguanidine (NTG), UV light or to a spontaneously occurring mutant.
  • EMS ethane methane sulphonate
  • NTG N-methyl-N'-nitro-N-nitroguanidine
  • variant should be understood as strain which is functionally equivalent to a strain of the invention, e.g. having substantially the same polysaccharide producing properties. Such variants, which may be identified using appropriate screening techniques, are a part of the present invention.
  • polysaccharides are purified from the bacteria according to the method described in International Dairy Journal 9 (1999) : Separation, purification and characterisation of extracellular polysaccharides produced by slime-forming Lactococcus lactis ssp cremoris strains.
  • the anti-inflammatory potential of the purified CPS/EPS are analysed in a murine dendritic cell assay and/or an assay involving a human intestinal epithelial cell line (HT-29).
  • the selected strains and the purified CPS/EPS are screened for immuno-modulatory and anti-inflammatory potential in murine bone marrow derived dendritic cells •
  • the selected strains are screened for immuno-modulatory and anti-inflammatory potential in human intestinal epithelial cell cultures (Caco-2 and/or HT-29).
  • Markers of particular relevance are IL-8 (pro-inflammatory cytokine), and NF-KB 1 and PPAR- ⁇ 2 (pro-inflammatory and anti-inflammatory transcription factors, respectively). These markers are measured in cell culture supernatants, and in cytoplasmic and nuclear extracts of the cells.
  • the anti-inflammatory potential of whole strains producing CPS/EPS are analysed in a murine dendritic cell assay and/or an assay involving a human intestinal epithelial cell line (HT-29).
  • NF- ⁇ B is a family of transcription factors composed of homo- or heterodimers. Transcription factor of many genes in both innate and adaptive immo ⁇ e responses.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Nutrition Science (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dispersion Chemistry (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

The present invention relates to a bacterial polysaccharide from a bacterium belonging to a species of the group consisting of Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium bifidum, Streptococcus thermophilus and Lactobacillus reuteri. The use of said polysaccharide for treatment of diseases, in particular inflammatory bowel diseases and pharmaceutical composition comprising such a polysaccharide.

Description

PHARMACEUTICALS COMPRISING A BACTERIAL POLYSACCHARIDE
FIELD OF INVENTION
The present invention relates to a bacterial polysaccharide, its use for treatment of diseases, and pharmaceutical composition comprising such a polysaccharide. SUMMARY OF INVENTION
The present inventors have shown that polysaccharide (CPS and/or EPS) producing lactic acid bacteria strains are able to inhibit a pro-inflammatory stimulation of cells in culture. Based on this surprising finding, it is contemplated that EPS may reduce gastric mucosal inflammation in humans and have a general beneficial effect on the human immune system. This inhibition was not observed by an isogenic strain that is unable to produce EPS. As the EPS seems to "shield-off" the cells in culture, it is contemplated that EPS are beneficial for patients suffering from a break-down in their intestinal barrier function, e.g. patients suffering from Crohns disease. The data suggests that EPS might be helpful for maintaining a healthy gastrointestinal function, i.e. improving intestinal mucosal barrier function, for subjects suffering from irritable bowel syndrome as well as for normal, healthy subjects. Further, the data suggests that EPS is able to influence the immune system (immune modulation), that EPS decreases or inhibit inflammatory responses (EPS has anti-inflammatory properties), and that EPS is able to maintain gut health by enhancing the intestinal mucosal barrier function. The beneficial effect of EPS will be applicable in a number of settings: o For healthy people wishing to improve intestinal health o For people suffering from intestinal complications, e.g. irritable bowel syndrome (IDS),
Crohn's disease, or colitis. o The CPS/EPS concept may be able to play a role during early life development
DETAILED DISCLOSURE In a first aspect, the present invention relates to a polysaccharide isolated from a bacterium belonging to a species of the group consisting of:
Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium bifidum, Streptococcus thermophilus, and Lactobacillus reuteri.
In a second aspect, the present invention relates to a polysaccharide isolated from the growth medium (e.g. supernatant) of a bacterium belonging to a species of the group consisting of: Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium bifidum, Streptococcus thermophilus, and Lactobacillus reuteri. In an interesting embodiment the growth medium may comprise milk from a mammal. It is presently preferred that the bacterium belongs to a strain selected from the group consisting of: BB-12 ® free (CHCC8902), BB-12 ® (CHCC5445), ST143 (CHCC2389), RC-14 ® (CHCC5151), Bb. Longum sp. (CHCC8879), ST6008 (CHCC6008), ST9204 (CHCC9204), ST4239 (CHCC4239), BB-02 (CHCC2228), and a mutant/variant of any of these.
It is contemplated that the polysaccharide is an extracellular polysaccharide (EPS) or a capsular polysaccharide (CPS).
In a further aspect, the present invention relates to a pharmaceutical composition comprising the polysaccharide of the invention, and to a pharmaceutical composition comprising a bacterium belonging to a species of the group consisting of:
Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium bifidum, Streptococcus thermophilus, and Lactobacillus reuteri, especially a pharmaceutical composition comprising a bacterium belonging to a strain selected from the group consisting of: BB-12 ® free (CHCC8902), BB-12 ® (CHCC5445), ST143 (CHCC2389), RC-14 ® (CHCC5151), Bb. Longum sp. (CHCC8879), ST6008 (CHCC6008), ST9204 (CHCC9204), ST4239 (CHCC4239), BB-02 (CHCC2228), and a mutant/variant of any of these. The pharmaceutical compositions which comprise living cells may further comprises a prebiotic or a growth medium, e.g. a growth medium which comprises milk from a mammal, either as a mixture or as a kit of parts, wherein the bacterial cells are packed separately from the prebiotic or growth medium.
In a still further aspect, the present invention relates to the use of a polysaccharide of the invention, or the pharmaceutical composition of the invention, for treatment of inflammatory disease. In an embodiment, the disease is inflammatory bowel disease, colitis, or Crohn's disease.
In another aspect, the present invention relates to a method of treatment of an inflammatory disease by administering a polysaccharide or a pharmaceutical composition of the invention to the person in need of treatment. The disease may be inflammatory bowel disease, colitis, or Crohn's disease.
DEFINITIONS
In the present context, the term "mutant" should be understood as a strain derived from a strain of the invention by means of e.g. genetic engineering, radiation and/or chemical treatment. It is preferred that the mutant is a functionally equivalent mutant, e.g. a mutant that has substantially the same, or improved, polysaccharide producing properties as the mother strain. Such a mutant is a part of the present invention. Especially, the term "mutant" refers to a strain obtained by subjecting a strain of the invention to any conventionally used mutagenization treatment including treatment with a chemical mutagen such as ethane methane sulphonate (EMS) or N-methyl-N'-nitro-N-nitroguanidine (NTG), UV light or to a spontaneously occurring mutant.
In the present context, the term "variant" should be understood as strain which is functionally equivalent to a strain of the invention, e.g. having substantially the same polysaccharide producing properties. Such variants, which may be identified using appropriate screening techniques, are a part of the present invention.
The use of the terms "a" and "an" and "the" and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms "comprising", "having", "including" and "containing" are to be construed as open-ended terms (i.e., meaning "including, but not limited to,") unless otherwise noted. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as") provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.
EXPERIMENTAL
Purification of polysaccharides The polysaccharides are purified from the bacteria according to the method described in International Dairy Journal 9 (1999) : Separation, purification and characterisation of extracellular polysaccharides produced by slime-forming Lactococcus lactis ssp cremoris strains.
Analysis of the in vitro anti-inflammatory potential of the purified CPS/EPS.
The anti-inflammatory potential of the purified CPS/EPS are analysed in a murine dendritic cell assay and/or an assay involving a human intestinal epithelial cell line (HT-29). o The selected strains and the purified CPS/EPS are screened for immuno-modulatory and anti-inflammatory potential in murine bone marrow derived dendritic cells • The selected strains are screened for immuno-modulatory and anti-inflammatory potential in human intestinal epithelial cell cultures (Caco-2 and/or HT-29). o Markers of particular relevance are IL-8 (pro-inflammatory cytokine), and NF-KB1 and PPAR-γ2 (pro-inflammatory and anti-inflammatory transcription factors, respectively). These markers are measured in cell culture supernatants, and in cytoplasmic and nuclear extracts of the cells.
Analysis of the in vitro anti-inflammatory potential of whole strains producing CPS/EPS.
• The anti-inflammatory potential of whole strains producing CPS/EPS are analysed in a murine dendritic cell assay and/or an assay involving a human intestinal epithelial cell line (HT-29).
Results
Figure imgf000005_0001
Preferred embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations of those preferred embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.
1 NF-κB is a family of transcription factors composed of homo- or heterodimers. Transcription factor of many genes in both innate and adaptive immoπe responses.
2 Nuclear hormone receptor. Activation of this transcription factor inhibits inflammatory gene expression (suppression of NF- B) REFERENCES
International Dairy Journal 9 (1999) : Separation, purification and characterisation of extracellular polysaccharides produced by slime-forming Lactococcus lactis ssp cremoris strains.
WO05021575A, WO07095958A, WO06119780A, WO05072641
All references cited in this patent document are hereby incorporated herein in their entirety by reference.

Claims

1. A polysaccharide isolated from a bacterium belonging to a species of the group consisting of:
Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium bifidum, Streptococcus thermophilus, and Lactobacillus reuteri.
2. A polysaccharide isolated from the growth medium (e.g. supernatant) of a bacterium belonging to a species of the group consisting of:
Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium bifidum, Streptococcus thermophilus, and Lactobacillus reuteri.
3. A polysaccharide of claim 2, wherein the growth medium comprises milk from a mammal.
4. The polysaccharide of any preceding claims, wherein the bacterium belongs to a strain selected from the group consisting of: BB-12 ® free (CHCC8902, DSM 17281), BB-12 ®
(CHCC5445, DSM 15954), ST143 (CHCC2389, ), RC-14 ® (CHCC5151), Bb. Longum sp. (CHCC8879), ST6008 (CHCC6008, DSM18111), ST9204 (CHCC9204), ST4239 (CHCC4239), BB-02 (CHCC2228), and a mutant/variant of any of these.
5. The polysaccharide of any preceding claim, which is selected from the group consisting of: an extracellular polysaccharide (EPS) or a capsular polysaccharide (CPS).
6. Pharmaceutical composition comprising the polysaccharide of any preceding claims.
7. Pharmaceutical composition comprising a bacterium belonging to a species of the group consisting of:
Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium bifidum, Streptococcus thermophilus, and Lactobacillus reuteri.
8. Pharmaceutical composition comprising a bacterium belonging to a strain selected from the group consisting of: BB-12 ® free (CHCC8902), BB-12 ® (CHCC5445), ST143 (CHCC2389), RC-14 ® (CHCC5151), Bb. Longum sp. (CHCC8879), ST6008 (CHCC6008), ST9204 (CHCC9204), ST4239 (CHCC4239), BB-02 (CHCC2228), and a mutant/variant of any of these.
9. Pharmaceutical composition of claim 7 or 8, which further comprises a prebiotic or a growth medium, e.g. a growth medium which comprises milk from a mammal.
10. Use of a polysaccharide of any preceding claims for treatment of inflammatory disease.
11. Use of a pharmaceutical composition of any preceding claims for treatment of inflammatory disease.
12. Use according to any preceding claim, where the disease is inflammatory bowel disease, colitis, or Crohn's disease.
13. Method of treatment of an inflammatory disease by administering a polysaccharide or a pharmaceutical composition of any preceding claims to the person in need of treatment.
14. Method according to the preceding claim, where the disease is inflammatory bowel disease, colitis, or Crohn's disease.
PCT/EP2009/060872 2008-08-28 2009-08-24 Pharmaceuticals comprising a bacterial polysaccharide WO2010023178A1 (en)

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WO2011004012A2 (en) 2009-07-10 2011-01-13 Chr. Hansen A/S Production of cottage cheese by using streptococcus thermophilus
WO2011092300A1 (en) 2010-01-28 2011-08-04 Chr. Hansen A/S Lactic bacterium for texturizing food products selected on basis of phage resistance
US20110223251A1 (en) * 2008-08-28 2011-09-15 Chr-Hansen A/S Bacterial composition
WO2012092155A1 (en) * 2010-12-31 2012-07-05 Abbott Laboratories Synbiotic combination of probiotic and human milk oligosaccharides to promote growth of beneficial microbiota
CN103409434A (en) * 2013-06-14 2013-11-27 中国农业大学 Bifidobacterium animalis EPS (Exopolysaccharide) biosynthetic gene cluster
US8703737B2 (en) 2010-12-31 2014-04-22 Abbott Laboratories Nutritional formulations including human milk oligosaccharides and antioxidants and uses thereof
US8802650B2 (en) 2010-12-31 2014-08-12 Abbott Laboratories Methods of using human milk oligosaccharides for improving airway respiratory health
US9283240B2 (en) 2010-12-31 2016-03-15 Abbott Laboratories Human milk oligosaccharides for modulating inflammation
US9453231B2 (en) 2010-10-22 2016-09-27 Chr. Hansen A/S Texturizing lactic acid bacteria strains
US9539269B2 (en) 2010-12-31 2017-01-10 Abbott Laboratories Methods for decreasing the incidence of necrotizing enterocolitis in infants, toddlers, or children using human milk oligosaccharides
US9763970B2 (en) 2010-12-31 2017-09-19 Abbott Laboratories Nutritional compositions comprising human milk oligosaccharides and nucleotides and uses thereof for treating and/or preventing enteric viral infection
US9795623B2 (en) 2010-12-31 2017-10-24 Abbott Laboratories Methods for reducing the incidence of oxidative stress using human milk oligosaccharides, vitamin C and anti-inflammatory agents
EP3295926A1 (en) 2016-09-19 2018-03-21 Institut Univ. de Ciència i Tecnologia, S.A. Exopolysaccharide-protein complex, a method of preparing said complex and uses thereof
US10639319B2 (en) 2011-08-29 2020-05-05 Abbott Laboratories Human milk oligosaccharides for preventing injury and/or promoting healing of the gastrointestinal tract
CN111560333A (en) * 2020-05-21 2020-08-21 浙江大学 Separation of extracellular polysaccharide of lactic acid bacteria and application thereof
US11337990B2 (en) 2010-12-31 2022-05-24 Abbott Laboratories Human milk oligosaccharides to promote growth of beneficial bacteria
WO2022243052A1 (en) 2021-05-18 2022-11-24 Chr. Hansen A/S Method of producing fermented milk products with improved texture and reduced post-acidification
EP3955938A4 (en) * 2019-04-19 2022-12-21 The Rockefeller University Unraveling receptor-metabolite interactions in the human microbiome
WO2023066163A1 (en) * 2021-10-21 2023-04-27 华南理工大学 Exopolysaccharide separated from lactobacillus delbrueckii and streptococcus thermophilus fermented yoghourt and application thereof

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