OA20887A - Compositions comprising bacterial strains. - Google Patents

Abstract

The invention provides compositions comprising one or more bacterial strains for treating or preventing sensory hypersensitivity.

Description

COMPOSITIONS COMPRISING BACTERIAL STRAINS

TECHNICAL FIELD

This invention is in the field of compositions comprising bacterial strains isolated from the mammalian digestive tract and the use of such compositions in the treatment of disease.

BACKGROUND TO THE INVENTION

The human intestine is thought to be stérile in utero, but it is exposed to a large variety of maternai and environmental microbes immediately after birth. Thereafter, a dynamic period of microbial colonization and succession occurs, which is mfluenced by factors such as delîvery mode, environment, diet and host génotype, ail of which impact upon the composition of the gut microbiota, particularly during early life. Subsequently, the microbiota stabilizes and becomes adult-lîke [1], The human gut microbiota contains more than 1,500 different phylotypes dominated in abundance levels by two major bacterial divisions (phyla), the Bacteroidetes and the Finnicutes [2-3]. The successful symbiotic relationships arising from bacterial colonization of the human gut hâve yielded a wide variety of metabolic, structural, protective and other bénéficiai funétions. The enhanced metabolic activîties of the colonized gut ensure that otherwise indigestible dietary components are degraded with release of by-products providing an important nutrient source for the host and additional health benefits. Similarly, the immunological importance of the gut microbiota is well-recognized and is exemplified in gennfree animais which hâve an impaired immune System that is functionally reconstituted following the introduction of commensal bacterîa [4-6].

Dramatic changes in microbiota composition hâve been documented in gastrointestinal disorders such as inflammatory bowel disease (IBD). For example, the levels of Clostridium cluster XlVa and Clostridium cluster XI (F. prausnitzii) bacterîa are reduced in IBD patients whilst numbers of E. coli are increased, suggesting a shift in the balance of symbionts and pathobionts withîn the gut [7-11].

In récognition of the potentîal positive effect that certain bacterial strains may hâve on the animal gut, varions strains hâve been proposed for use in the treatment of various diseases (see, for example, [12-15]). A number of strains, including mostly Lactobacillus and Bifidobacterium strains, hâve been proposed for use in treating various bowel disorders (see [16] for a review). Strains of the genus Blautia hâve also been proposed for use in modulating the microbial balance of the digestive ecosystem [17]. However, the relationshîp between different bacterial strains and different dîseases, and the précisé effects of particular bacterial strains on the gut and at a systemic level and on any particular types of diseases, are poorly characterised.

There is a requirement for the potential effects of gut bacteria to be characterised so that new thérapies using bacteria can be developed.

SUMMARY OF THE INVENTION

The inventors hâve developed new thérapies for treating and preventing sensory hypersensitivity, allodynia and/or hyperalgesia. In particular, the invention provides a composition comprising a bacterial strain of the genus Blautia for use in a method of treating or preventing sensory hypersensitivity. Additionally, the invention provides a method of treating or preventing 10 allodynia and/or hyperalgesia, comprising administering a composition comprising a bacterial strain of the genus Blautia.

Furthermore, the invention provides a use of a composition comprising a bacterial strain of the genus Blautia for the manufacture of a médicament for the treatment or prévention of allodynia and/or hyperalgesia.

Sensory hypersensitivity is frequently associated with allodynia and/or hyperalgesia and the inventors hâve identified that bacterial strains from the genus Blautia can be effective for reducing allodynia and/or hyperalgesia. Therefore, in one embodiment, the invention provides a composition comprising a bacterial strain of the genus Blautia, for use in a method of treating or preventing allodynia and/or hyperalgesia. As described in the examples, oral administration of 20 compositions comprising Blautia hydrogenotrophica may reduce allodynia in an animal model of fibromyalgia.

The use of organisme from the genus Blautia to treat viscéral hypersensitivity has been disclosed in International Patent Publication No. WO2017/148596. However, as explained in more detail below, viscéral hypersensitivity and allodynia/hyperalgesia hâve different pathophysiologies and 25 causes. Accordingly, that publication does not suggest that such organisais can be successfully used to treat allodynia and/or hyperalgesia.

In preferred embodiments, the invention provides a composition comprising a bacterial strain of the genus Blautia, for use in treating or preventing sensory hypersensitivity in a subject diagnosed with neuropathy, complex régional pain syndrome, postherpetic neuralgia, 30 fibromyalgia, or migraine. Particularly preferred embodiments provide compositions comprising a bacterial strain of the genus Blautia for treating or preventing allodynia and/or hyperalgesia. In a preferred embodiment, the composition is for use in treating or preventing allodynia and/or hyperalgesia in a subject diagnosed with fîbromyalgia. The inventors hâve shown that the compositions of the invention work particularly well in a model of fîbromyalgia.

In preferred embodiments of the invention, the bacterial straîn in the composition is of Blautia hydrogenotrophica. The bacterial strains may hâve a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to the 16s rRNA sequence of a bacterial strain of Blautia hydrogenotrophica. Preferably, the bacterial strain has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO:5. Most preferably, the bacterial strain in the composition is the Blautia hydrogenotrophica strain deposited under accession number DSM 14294. Preferably, the bacterial strain for use in the invention has the 16s rRNA sequence represented by SEQ ID NO:5. In other embodiments, the bacterial strain in the composition has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO: 5.In further embodiments of the invention, the bacterial strain in the composition is of Blautia stercoris. The bacterial strains may hâve a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to the 16s rRNA sequence of a bacterial strain of Blautia stercoris. Preferably, the bacterial strain has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO:1 or 3. Preferably, the sequence identity is to SEQ ID NO:3. Preferably, the bacterial strain for use in the invention has the 16s rRNA sequence represented by SEQ ID NO:3. In other embodiments, the bacterial strain in the composition has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO: 1 or 3.

In further embodiments of the invention, the bacterial strain in the composition is of Blautia wexlerae. Closely related strains may also be used, such as bacterial strains that hâve a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to the 16s rRNA sequence of a bacterial strain of Blautia wexlerae. Preferably, the bacterial strain has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO:2 or 4. Preferably, the sequence identity is to SEQ ID NO:4. Preferably, the bacterial strain for use în the invention has the I6s rRNA sequence represented by SEQ ID NO:4. in other embodiments, the bacterial strain in the composition has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO: 4.

In further embodiments of the invention, the bacterial strain in the composition is of Blautia producta. Closely related strains may also be used, such as bacterial strains that hâve a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to the 16s rRNA sequence of a bacterial strain of Blautia producta. Preferably, the bacterial strain has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO:6. Preferably, the bacterial strain for use in the invention has the 16s rRNA sequence represented by SEQ ID NO:6. In other embodiments, the bacterial strain in the composition has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO: 6.

In further embodiments of the invention, the bacterial strain in the composition is of Blautia coccoides. Closely related straîns may also be used, such as bacterial strains that hâve a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to the 16s rRNA sequence of a bacterial strain of Blautia coccoides. Preferably, the bacterial strain has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO:7 or 8. Preferably, the bacterial strain for use in the invention has the 16s rRNA sequence represented by SEQ ID NO:7 or 8. In other embodiments, the bacterial strain in the composition has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO: 7 or 8.

In certain embodiments, the composition of the invention is for oral administration. Oral administration is convenient for patients and practitioners and aliows delîvery to and/or partial or total colonisation of the intestine.

In certain embodiments, the composition of the invention comprises one or more pharmaceutically acceptable excipients or carriers.

In certain embodiments, the composition of the invention has been lyophilised. The composition of the invention can also comprise a lyophilised bacteria strain of the genus Blautia. Lyophilisation is an effective and convenient technique for preparing stable compositions that allow delivery of bacteria, and is shown to provide effective compositions in the examples.

In certain embodiments, the invention provides a food product comprising the composition comprising a bacterial strain of the genus Blautia as described above.

In certain embodiments, the invention provides a vaccine composition comprising the composition comprising a bacterial strain of the genus Blautia as described above.

BRIEF DESCRIPTION OF DRAWINGS

Figure 1: Weight gain over time. Error bars dénoté SEM.

Figure 2: Somatosensory responses (hindpaw placing). Asterisks indicate statistically significant différences from the appropriate contralatéral response. Error bars dénoté SEM. Normal Control N = 12, Disease Control N = 24, Blautia hydrogenotrophica N = 12, Lyobuffer N = 12.

Figure 3: Mechanical allodynia response (50% paw withdrawal threshold) in rat model of fibromyalgia. Error bars dénoté SEM. N = 12 per group.

Figure 4: Muscle compression withdrawal threshold testing. Error bars dénoté SEM. N = 12 per group.

DISCLOSURE OF THE INVENTION

Bacterial strains

The compositions of the invention comprise a bacterial strain of the genus Blautia. The examples demonstrate that bacteria of this genus are useful for treating or preventing sensory hypersensitivity and are partîcularly useful for treating or preventing allodynia and/or hyperalgesia. The preferred bacterial strains are of the species Blautia hydrogenotrophica, Blautia stercoris and Blautia wexlerae. Other bacterial strains for use in the invention are Blautia producta, Blautia coccoides and Blautia hansenii albeit, in some embodiments, the composition may not comprise Blautia producta.

Ex amples of Blautia strains for use in the invention include Blautia hydrogenotrophica, B. stercoris, B. faecis, B. coccoides, B. glucerasea, B. hansenii, B. luti, B. producta, B. schinkii and B. wexlerae. The Blautia species are Gram-reaction-positive, non-motile, non-spore forming bacteria that may be either coccoid or oval and ail are obligate anaerobes that produce acetic acid as the major end-product of glucose fermentation [18], Blautia may be isolated from the human gut, although B. producta was isolated from a septicaemia sample.

Blautia hydrogenotrophica (previously known as Ruminococcus hydrogenotrophicus) has been isolated from the guts of mammals, is strictly anaérobie, and métabolisés H₂/CO₂ to acetate, which may be important for human nutrition and health. The type strain of Blautia hydrogenotrophica is S5a33 = DSM 10507 = JCM 14656. The GenBank accession number for the 16S rRNA gene sequence of Blautia hydrogenotrophica strain S5a36 is X95624.1 (disclosed herein as SEQ ID NO:5). This exemplary Blautia hydrogenotrophica strain is described in [18] and [19]. The S5a33 strain and the S5a36 strain correspond to two subclones of a strain isolated from a faecal sample of a healthy subject. They show identical morphology, physiology and metabolism and hâve identical 16S rRNA sequences. Thus, in some embodiments, the Blautia hydrogenotrophica for use in the invention has the 16S rRNA sequence of SEQ ID NO:5.

The Blautia hydrogenotrophica bacterium deposîted under accession number DSM 14294 was tested in the examples and is also referred to herein as strain BH. Strain BH was deposîted with the Deutsche Sammlung von Mikroorganismen [German Microorganism Collection] (Mascheroder Weg 1b, 38124 Braunschweig, Germany) in January 1996 as “Ruminococcus hydrogenotrophicus” under accession number DSM 14294 as “S5a33” on lOth May 2001. The depositor was INRA Laboratoire de Microbiologie CR de Clermont-Ferrand/Theix 63122 Saint Genès Champanelle, France. Ownership of the deposits has passed to 4D Pharma Pic by way of assignment.

The GenBank accession number for the 16S rRNA gene sequence of Blautia stercoris strain GAM6-1^T is HM626177 (disclosed herein as SEQ ID NO:1). An exemplary Blautia stercoris strain is described in [20]. The type strain of Blautia wexlerae is WAL 14507 = ATCC BAA1564 = DSM 19850 [18], The GenBank accession number for the 16S rRNA gene sequence of Blautia wexlerae strain WAL 14507 T is EF036467 (disclosed herein as SEQ ID NO:2). This exemplary Blautia wexlerae strain is described in [18].

A preferred Blautia stercoris strain is the strain deposîted under accession number NCIMB 42381, which is also referred to herein as strain 830. A 16S rRNA sequence for the 830 strain is provided in SEQ ID NO:3. Strain 830 was deposîted with the international depositary authority NCIMB, Ltd. (Ferguson Building, Craibstone Estate, Bucksburn, Aberdeen, AB21 9YA, Scotland) by GT Biologics Ltd. (Life Sciences Innovation Building, Aberdeen, AB25 2ZS, Scotland) on 12th March 2015 as “Blautia stercoris 830” and was assigned accession number NCIMB 42381. GT Biologics Ltd. subsequently changed its name to 4D Pharma Research Limited.

A preferred Blautia wexlerae strain is the strain deposîted under accession number NCIMB 42486. A 16S rRNA sequence for this strain is provided in SEQ ID NO:4. The strain was deposîted with the international depositary authority NCIMB, Ltd. (Ferguson Building, Craibstone Estate, Bucksburn, Aberdeen, AB21 9YA, Scotland) by 4D Pharma Research Ltd. (Life Sciences Innovation Building, Aberdeen, AB25 2ZS, Scotland) on 16th November 2015 as “Blautia/Ruminococcus” and was assigned accession number NCIMB 42486.

A preferred Blautia producta strain for use in the invention is the strain deposîted under accession number NCIMB 43170 with international depositary authority NCIMB, Ltd. (Ferguson Building, Craibstone Estate, Bucksburn, Aberdeen, AB21 9YA, Scotland) by 4D

Pharma Research Limited (Life Sciences Innovation Building, Aberdeen, AB25 2ZS, Scotland) on 20th August 2018 as “Blautia producta”.

Bacterial strains closely related to the strain tested in the examples are also expected to be effective for treating or preventing allodynîa and/or hyperalgesia. In certain embodiments, the bacterial strain for use in the invention has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to the 16s rRNA sequence of a bacterial strain of Blautia hydrogenotrophica. Preferably, the bacterial strain for use in the invention has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO:5.

In certain embodiments, the bacterial strain for use in the invention has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to the 16s rRNA sequence of a bacterial strain of Blautia stercoris. Preferably, the bacterial strain for use in the invention has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO:1 or SEQ ID NO:3. Preferably, the sequence identity is to SEQ ID NO:3. Preferably, the bacterial strain for use in the invention has the 16s rRNA sequence represented by SEQ ID NO;3.

In certain embodiments, the bacterial strain for use in the invention has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to the 16s rRNA sequence of a bacterial strain of Blautia wexlerae. Preferably, the bacterial strain for use in the invention has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO:2 or SEQ ID NO:4. Preferably, the sequence identity is to SEQ ID NO:4. Preferably, the bacterial strain for use in the invention has the 16s rRNA sequence represented by SEQ ID NO:4.

In certain embodiments, the bacterial strain for use in the invention has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to the 16s rRNA sequence of a bacterial strain of Blautia producta. Preferably, the bacterial strain for use in the invention has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO:6. Preferably, the bacterial strain for use in the invention has the 16s rRNA sequence represented by SEQ ID NO:6.

In certain embodiments, the bacterial strain for use in the invention has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to the I6s rRNA sequence of a bacterial strain of Blautia coccoides. Preferably, the bacterial strain for use in the invention has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO:7 or 8. Preferably, the bacterial strain for use in the invention has the 16s rRNA sequence represented by SEQ ID NO:7 or 8.

Bacterial strains that are biotypes of the bacterium deposited under accession number DSM 14294 or biotypes of the bacteria deposited under accession numbers NCIMB 42381, NCIMB 42486, and NCIMB 43170 are also expected to be effective for treating or preventing allodynia and/or hyperalgesia. A biotype is a closely related strain that has the same or very similar physiological and biochemical characteristics.

Strains that are biotypes of a bacterium deposited under accession number DSM 14294, NCIMB 42381, NCIMB 42486, or NCIMB 43170 and that are suîtable for use in the invention may be identified by sequencing other nucléotide sequences for a bacterium deposited under accession number DSM 14294, NCIMB 42381, NCIMB 42486 or NCIMB 43170. For example, substantially the whole genome may be sequenced and a biotype strain for use in the invention may hâve at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% sequence identity across at least 80% of its whole genome (e.g. across at least 85%, 90%, 95% or 99%, or across its whole genome). For example, in some embodiments, a biotype strain has at least 98% sequence identity across at least 98% of its genome or at least 99% sequence identity across 99% of its genome. Other suitable sequences for use in identifying biotype strains may include hsp60 or répétitive sequences such as BOX, ERIC, (GTGk, or REP [21]. Biotype strains may hâve sequences with at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% sequence identity to the corresponding sequence of a bacterium deposited under accession number DSM 14294, NCIMB 42381, NCIMB 42486, or NCIMB 43170. In some embodiments, a biotype strain has a sequence with at least 97%, 98%, 99%, 99.5% or 99.9% sequence identity to the 16S rRNA sequence of SEQ ID NO:5.

Altematively, strains that are biotypes of a bacterium deposited under accession number DSM 14294, NCIMB 42381, NCIMB 42486 or NCIMB 43170 and that are suitable for use in the invention may be identified by using the accession number DSM 14294 deposit, the accession number NCIMB 42381 deposit, the accession number NCIMB 42486 deposit, or the accession number NCIMB 43170 deposit, and restriction fragment analysis and/or PCR analysis, for example by using fluorescent amplified fragment length polymorphism (FAFLP) and répétitive DNA element (rep)-PCR fingerprinting, or protein profiling, or partial 16S or 23s rDNA sequencing. In preferred embodiments, such techniques may be used to identify other Blautia hydrogenotrophica, Blautia stercoris or Blautia wexlerae strains.

In certain embodiments, strains that are biotypes of a bacterium deposîted under accession number DSM 14294, NCIMB 42381, NCIMB 42486, or NCIMB 43170 and that are suitable for use in the invention are strains that provide the same pattern as a bacterium deposîted under accession number DSM 14294, NCIMB 42381, NCIMB 42486 or NCIMB 43170 when analysed by amplified ribosomal DNA restriction analysis (ARDRA), for example when using Sau3AI restriction enzyme (for exemplary methods and guidance see, for example [22]). Alternatively, biotype strains are identified as strains that hâve the same carbohydrate fermentation patterns as a bacterium deposîted under accession number DSM 14294, NCIMB 42381, NCIMB 42486 or NCIMB 43170.

Other Blautia strains that are useful in the invention, such as biotypes of a bacterium deposîted under accession number DSM 14294, NCIMB 42381 NCIMB 42486, or NCIMB 43170 may be identified using any appropriate method or strategy, încluding the assays described in the examples. For instance, strains for use in the invention may be identified by culturing bacteria and administering them to rats before testing in the Von Frey microfilament assay. In particular, bacterial strains that hâve siinîlar growth patterns, metabolic type and/or surface antigens to a bacterium deposîted under accession number DSM 14294, NCIMB 42381, NCIMB 42486 or NCIMB 43170 may be useful in the invention. A useful straîn will hâve comparable activity to the DSM 14294, NCIMB 42381, NCIMB 42486 or NCIMB 43170 strain as assessed, for example, b y the Von Frey micro filament assay. In particular, a biotype strain will elicit comparable effects on the fibromyalgia model to the effects shown in the ex amples, which may be identified by using the culturing and administration protocole described in the examples.

A particularly preferred strain of the invention îs the Blautia hydrogenotrophica strain deposîted under accession number DSM 14294. This is the exemplary strain tested in the examples and shown to be effective for treating disease. Therefore, the invention provides a cell, such as an isolated cell, of the Blautia hydrogenotrophica strain deposîted under accession number DSM 14294, or a dérivative thereof, for use in therapy, in particular for the diseases described herein.

A dérivative of the strain deposîted under accession number DSM 14294, NCIMB 42381, NCIMB 42486, or NCIMB 43170 may be a daughter strain (progeny) or a strain cultured (subcloned) from the original. A dérivative of a strain of the invention may be modîfied, for ex ample at the genetic level, wîthout ablating the biological activity. In particular, a dérivative strain of the invention is therapeutically active. A dérivative strain will hâve comparable microbiota modulatory activity to the original DSM 14294, NCIMB 42381, NCIMB 42486, NCIMB 43170 strain. In particular, a dérivative strain will elicit comparable effects on the allodynia and/or hyperalgesia inodel to the effects shown in the examples, which may be identified by using the culturing and administration protocols described in the examples. A dérivative of the DSM 14294 strain will generally be a biotype of the DSM 14294 strain. A dérivative ofthe NCIMB 42381 strain will generally be a biotype of the NCIMB 42381 strain. A dérivative ofthe NCIMB 42486 strain will generally be a biotype of the NCIMB 42486 strain. A dérivative of the NCIMB 43170 strain will generally be a biotype of the NCIMB 43170 strain.

The bacterial strain may also be a strain that has the saine safety and therapeutic efficacy characteristics as the strains deposited under accession number DSM 14294, NCIMB 42381, NCIMB 42486 or NCIMB 43170 and such cells are encompassed by the invention.

In preferred embodiments, the bacterial strains in the compositions of the invention are viable and capable of partially or totally colonising the intestine.

Therapeutic uses

In preferred embodiments, the compositions of the invention are for use în treating sensory hypersensitivity. They may be used for treating allodynia and/or hyperalgesia. Preferabiy, the compositions of the invention are for use in treating allodynia, in particular allodynia associated with fibromyalgia, as the inventors hâve seen good effects for this, as shown in the examples.

There are three main types of pain pathophysîology—nociceptive, neuropathie and sensory hypersensitivity. Sensory hypersensitivity describes a type of pain that exists without an identifiable nerve or tissue damage. This type of pain is thought to be a resuit of persistent dysfonction of neurons throughout the CNS that leads to lowering of pain thresholds and amplification of sensory signais. It is referred to by many names including centralized, dysfonctîonal, or idiopathic pain, central sensitization, and central sensitivity syndromes. The hallmark of this type of pain appears to be general îzed hypersensitivity to a variety of stimuli including mechanical, thermal, olfactory, auditory, and visual eues. Sensory hypersensitivity conditions include: Fibromyalgia, Irritable bowel syndrome, Tension-type headaches, Interstitial cystitis/pelvic pain syndrome, Tempo-mandibular joint disorder, Chronic fatigue syndrome, Restless leg syndrome and Neck and back pain without structural pathology [23].

Patients suffering from neuropathie pain and sensory hypersensitivity can be discriminated between using the Chronic Pain Questions according to ref [24] and the severity of the sensory hypersensitivity can be assessed using the Sensory Hypersensitivity Scale described in ref [25].

Allodynia (pain resulting from a non-painful stimulus) and hyperalgesia (increased sensitivity to pain) are commonly associated with sensory hypersensitivity, a tenu used to describe pain in the absence of identifiable damage to nerves or other tissues. Allodynia and hyperalgesia are hypothesized to be the resuit of persistent neuronal dysrégulation or dysfonction. These are frequently associated with a variety of conditions, including neuropathy, complex régional pain syndrome, postherpetic neuralgia, fibromyalgia, or migraine. The compositions of the invention can be used to treat a subject diagnosed with one or more of these conditions.

In a preferred embodiment, the compositions of the invention are for use in treating a subject diagnosed with fibromyalgia, in partîcular for treating a subject diagnosed with allodynia associated with fibromyalgia. These embodiments are preferred because the inventors hâve seen good effects with the compositions of the invention in a rat model of fibromyalgia. The examples demonstrate the abiiity of compositions of the invention to hâve bénéficiai effects on several factors that are conducive to proinoting a more positive outcome in a rat model of fibromyalgia. These include increased weight gain, improved performance in somatosensory testing and a réduction in mechanical allodynia.

Fibromyalgia is generally believed to be the resuit of sensory hypersensîtîvity, a tenn used to describe pain in the absence of identifiable damage to nerves or other tissues. This type of pain is hypothesized to be the resuit of persistent neuronal dysrégulation or dysfunction. As a resuit of the sensory hypersensîtîvity, patients expérience allodynia and hyperalgesia. Fibromyalgia is generally characterîzed by chronic pain and fatigue as well as sensitivity/tenderness in the joints and muscle tissue and many people with fibromyalgia also report sensîtivity to light, headaches and migraine attacks as symptoms or co-morbidities of the condition.

In contrast to sensory hypersensîtîvity, viscéral hypersensîtîvity is the term used to describe the expérience of pain within the inner organs at a level that is more intense than normal. This type of pain is related to the damage of somatic or viscéral tissue, due to trauma or inflammation, and is known as nociceptive pain. Nociceptive pain originales from outside of the nervous System and the nerve cells transmitting the pain impulses are believed to be functioning normally. Interestingly, viscéral hypersensîtîvity is a hallmark characteristic of Irritable Bowel Syndrome (IBS). While IBS is sometimes found in sufferers of fibromyalgia, it has been shown, for example in reference [26], that fibromyalgia patients do not usually suffer from viscéral hypersensîtîvity. In other words, fibromyalgia and viscéral hypersensîtîvity are discrète components of different conditions with different causes and pathophysiologies.

As demonstrated in the examples, bacterial compositions of the invention may be effective for reducing allodynia and/or hyperalgesia, in partîcular in a patient diagnosed with fibromyalgia. In embodiments, the patient does not suffer from viscéral hypersensitivity. In this respect, “suffer” means that a patient has either been formally diagnosed at the time of treatment or a patient who has not yet received a formai diagnosis but who expériences symptoms of the disease.

In preferred embodiments, the compositions of the invention are for use in treating or preventîng allodynia and/or hyperalgesia in a subject diagnosed with neuropathy, complex régional pain syndrome, postherpetic neuralgia, fibromyalgia, or migraine. In preferred embodiments, the compositions of the invention are for use in treating or preventing allodynia and/or hyperalgesia in a subject diagnosed with fibromyalgia.

Treatment or prévention of allodynia and/or hyperalgesia may refer to, for ex ample, an alleviation of the severity of symptoms or a réduction in the frequency of exacerbations or the range of triggers that are a problem for the patient. For example, in some embodiments the composition of the invention is for use in treating or preventing severe allodynia and/or hyperalgesia. In some embodiments the subject having severe allodynia and/or hyperalgesia is a subject diagnosed with neuropathy, complex régional pain syndrome, postherpetic neuralgia, fibromyalgia, or migraine. In some embodiments the subject having severe viscéral hypersensitivity is a subject diagnosed with fibromyalgia.

In some embodiments, the sensory hypersensitivity (e.g. the allodynia and/or hyperalgesia) is not caused b y an autoimmune disease. Furthermore, in some embodiments the subject having sensory hypersensitivity (e.g. severe allodynia and/or hyperalgesia) is a subject diagnosed with neuropathy, wherein the neuropathy is not caused by an autoimmune disease.

Modes of administration

Preferably, the compositions of the invention are formulated to be administered to the gastrointestinal tract in order to enable delivery to and/or partial or total colonisation of the intestine with the bacterial strain of the invention. In some embodiments, the terni “total colonisation of the intestine” means that bacteria hâve colonised ail parts of the intestine (i.e. the small intestine, large intestine and rectum). In further embodiments of the invention, the terni “total colonisation” or “partial colonisation” means that the bacteria are retained permanently or temporarily in the intestine, respectively. Generally, the compositions of the invention are administered orally, but they may be administered rectal]y, intranasally, or via buccal or sublingual routes.

In certain embodiments, the compositions of the invention may be administered as a foam, as a spray or a gel.

In certain embodiments, the compositions of the invention may be adminîstered as a suppository, such as a rectal suppository, for example in the form of a theobroma oil (cocoa butter), synthetic hard fat (e.g. suppocîre, witepsol), glycero-gelatin, polyethylene glycol, or soap glycerin composition.

In certain embodiments, the compositions of the invention are adminîstered to the gastrointestinal tract via a tube, such as a nasogastric tube, orogastric tube, gastric tube, jejunostomy tube (J tube), percutaneous endoscopie gastrostomy (PEG), or a port, such as a chest wall port that provides access to the stomach, jéjunum and other suitable access ports.

The compositions of the invention may be adminîstered once, or they may be adminîstered sequentially as part of a treatment regimen. In certain embodiments, the compositions of the invention are to be adminîstered daîly (either once or several times).

In certain embodiments, the compositions of the invention are adminîstered regularly, such as daîly, every two days, or weekly, for an extended period of time, such as for at least one week, two weeks, one month, two months, six months, or one year.

In some embodiments the compositions of the invention are adminîstered for 7 days, 14 days, 16 days, 21 days or 28 days or no more than 7 days, 14 days, 16 days, 21 days or 28 days. For example, in some embodiments the compositions of the invention are adminîstered for 16 days.

In certain embodiments of the invention, treatment according to the invention is accompanied by assessment of the patient’s gut microbiota. Treatment may be repeated if delîvery of and/or partial or total colonisation with the strain of the invention is not achieved such that efficacy is not observed, or treatment may be ceased if delîvery and/or partial or total colonisation is successful, and efficacy is observed.

In certain embodiments, the composition of the invention may be adminîstered to a prégnant animal, for example a mammal such as a human in order to prevent allodynia and/or hyperalgesia developing in her child in utero and/or after it is bom.

The compositions of the invention may be adminîstered to a patient that has been diagnosed with sensory hypersensitivity. They may also be adminîstered to a patient that has been diagnosed with allodynia and/or hyperalgesia or a disease or condition associated with allodynia and/or hyperalgesia (in particular fibromyalgia), or that has been identified as being at risk of allodynia and/or hyperalgesia. The compositions may also be adminîstered as a prophylactîc measure to prevent the development of allodynia and/or hyperalgesia in a healthy patient.

The compositions of the invention may be administered to a patient that has been Îdentified as having an abnormal gut microbîota. For ex ample, the patient may hâve reduced or absent colonisation by Blautia, and in particular Blautia hydrogenotrophica, Blautia stercoris, Blautia wexlerae, Blautia producta or Blautia coccoides.

The compositions of the invention may be administered as a food product, such as a nutritional supplément.

Generally, the compositions of the invention are for the prévention or treatment of humans, although they may be used to treat animais including monogastric mammals such as poultry, pigs, cats, dogs, horses or rabbits. The compositions of the invention may be useful for enhancing the growth and performance of animais. If administered to animais, oral gavage may be used.

In some embodiments, the subject to whom the composition is to be administered is an adult human. In some embodiments, the subject to whom the composition is to be administered is an infant human.

Compositions

The compositions of the invention comprise bacterîa. The inventors hâve îdentified the surprising ability of bacterîa from the genus Blautia to treat or prevent sensory hypersensitîvity. However, in order for bacterîa from the genus Blautia to exert their bénéficiai effect they need to be effectively delivered alive and/or viable to the small intestine. In general, a composition of the invention therefore does not comprise inactivated bacterîa of the species Blautia, in particular heat-inactivated bacterîa of the species Blautia.

The composition of the invention comprises bacterîa. In preferred embodiments of the invention, the composition is formulâted in freeze-dried form. The composition of the invention may comprise granules or gelatin capsules, for example hard gelatin capsules, comprising a bacterial strain of the invention.

Preferabiy, the composition of the invention comprises lyophîlîsed bacterîa. Lyophilisation of bacterîa is a well-established procedure and relevant guidance is available in, for example, references [27-29]. The examples demonstrate that lyophilised compositions are particularly effective.

Altematively, the composition of the invention may comprise a live, active bacterial culture. The examples demonstrate that cultures of the bacterîa of the invention are therapeutically effective.

In some embodiments, the bacterial strain in the composition of the invention has not been inactivated, for example, has not been heat-inactivated. In some embodiments, the bacterial strain in the composition of the invention has not been killed, for example, has not been heatkilled. In some embodiments, the bacterial strain in the composition of the invention has not been attenuated, for example, has not been heat-attenuated. For example, in some embodiments, the bacterial strain in the composition of the invention has not been killed, inactivated and/or attenuated. For example, in some embodiments, the bacterial strain in the composition of the invention is live. For example, in some embodiments, the bacterial strain in the composition of the invention is viable. For example, in some embodiments, the bacterial strain in the composition of the invention is capable of parti al ly or totally colonising the intestine. For example, in some embodiments, the bacterial strain in the composition of the invention is viable and capable of partially or totally colonising the intestine.

The bacterial strain in the composition of the invention is preferably viable. Preferably it is capable of partially or totally colonising the intestine. The bacterial strain in the composition of the invention may be live and viable. The bacterial strain in the composition of the invention may be live, viable and capable of partially or totally colonising the intestine.

In some embodiments, the composition comprises a mixture of live bacterial strains and bacterial strains that hâve been killed. The invention provides compositions which are fonnulated to prevent the bacteria from being degraded or absorbed in the upper digestive tract and being unable to exert their effect. For example, the compositions may comprises oxygen scavengers and/or prebiotic substrates, such as vitamin C and non-digestible carbohydrates.

In addition, the composition can be enterically fonnulated. This ensures that the bacteria are not degraded on the way to the small intestine.

In preferred embodiments, the composition of the invention is encapsulated to enable delivery of the bacterial strain to the intestine. Encapsulation protects the composition from dégradation until delivery at the target location through, for example, rupturing with Chemical or physical stimuli such as pressure, enzymatic activity, or physical disintegratîon, which may be triggered by changes in pH. Any appropriate encapsulation method may be used. Exemplary encapsulation techniques include entrapment within a porous matrix, attachment or adsorption on solid carrier surfaces, self-aggregation by flocculation or with cross-linking agents, and mechanical containment behind a microporous membrane or a microcapsule. Guidance on encapsulation that may be useful for preparing compositions of the invention is available in, for example, référencés [30-31],

The composition may be administered orally and may be in the form of a tablet, capsule or powder. Encapsulated products are preferred because Blautia are anaerobes.

A composition of the invention includes a therapeutîcally effective amount of a bacterial strain of the invention. A therapeutîcally effective amount of a bacterial strain is sufficient to exert a bénéficiai effect upon a patient. A therapeutîcally effective amount of a bacterial strain may be sufficient to result in delivery to and/or partial or total colonisation of the patient’s intestine.

A suitable daily dose of the bacteria, for example for an adult human, may be from about 1 x I0³ to about 1 x 10’¹ colony forming units (CFU); for example, from about 1 x 10⁷ to about 1 x 10¹⁰ CFU; in another example from about 1 x 10⁶ to about 1 x 10¹⁰ CFU; in another example from about 1 x 10⁷ to about 1 x 10¹¹ CFU; m another example from about 1 x 10^s to about 1 x 10¹⁰ CFU; in another example from about 1 x 10^s to about 1 x 10¹¹ CFU.

In certain embodiments, the dose of the bacteria is at least 10⁹ cells per day, such as at least 10¹⁰, at least 10¹¹, or at least I0¹² cells per day.

A dose of the composition may comprise the bacterial strain from about 1 x 10⁶ to about 1 x 10¹¹ colony forming units (CFU) /g, respect to the weight of the composition. The dose may be suitable for an adult human. For example, the composition may comprise the bacteria] strain from about 1 x 10³ to about 1 x 10^!l CFU/g; for example, from about 1 x 10⁷ to about 1 x 10¹⁰ CFU/g; in another example from about 1 x I0⁶ to about i x 10¹⁰ CFU/g; in another example from about 1 x 10⁷ to about 1 x 10¹¹ CFU/g; in another example from about 1 x 10⁸ to about 1 x 10¹⁰ CFU/g; in another example from about 1 x 10^s to about 1 x I0^H CFU/g, from about I x 10⁸ to about 1 x 10¹⁰ CFU/g, The dose may be, for example, 1g, 3g, 5g, and 10g. The composition may be formulated as a probiotic. A probiotic is defined by the FAO/WHO as a live microorganism that, when administered in adéquate amounts, confers a health benefit on the host.

Typically, a probiotic, such as the composition of the invention, is optionally combined with at least one suitable prebiotic compound. In certain embodiments, the probiotic composition of the présent invention includes a prebiotic compound in an amount of from about 1 to about 30% by weight, respect to the total weight composition, (e.g. from 5 to 20% by weight), Known prebiotics include commercial products such as inulin and transgaiacto-oligosaccharides.

A prebiotic compound is usually a non-digestible carbohydrate such as an oligo- or polysaccharide, or a sugar alcohol, which is not degraded or absorbed in the upper digestive tract. The carbohydrate may be selected from the group consisting of: fructo-oligosaccharides (or FOS), short-chain fructo-oligosaccharides, inulin, isomalt-oligosaccharides, pectins, xylooligosaccharides (or XOS), chitosan-oligosaccharides (or COS), beta-glucans, arable gum modified and résistant starches, polydextrose, D-tagatose, acacia fibers, carob, oats, and citrus fibers. In one aspect, the prebiotics are the short-chain fructo-oligosaccharides (for simplicity shown herein below as FOSs-c.c); said FOSs-c.c. are not digestible carbohydrates, generally obtained by the conversion of the beet sugar and including a saccharose molécule to which three glucose molécules are bonded.

Other prebiotic compounds (such as vitamin C, for example), may be included as oxygen scavengers and to improve the delivery and/or partial or total colonisation and survival in vivo. Alternative!y, the probiotic composition of the invention may be administered orally as a food or nutritional product, such as milk or whey based fermented dairy product, or as a phannaceutical product.

The compositions of the invention may comprise pharmaceutically acceptable excipients or carriers. Examples of such suitable excipients may be found in the reference [32], Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art and are described, for example, in reference [33], Examples of suitable carriers include lactose, starch, glucose, methyl cellulose, magnésium stéarate, mannitol, sorbitol and the like. Examples of suitable diluents include éthanol, glycerol and water. The choice of pharmaceutical carrier, excipient or diluent can be selected with regard to the intended route of administration and standard pharmaceutical practice. The pharmaceutical compositions may comprise as, or in addition to, the carrier, excipient or diluent any suitable binder(s), fabricant (s), suspending agent(s), coating agent(s), solubilising agent(s). Exampies of suitable binders include starch, gelatin, natural sugars such as glucose, anhydrous lactose, free-flow lactose, beta-lactose, corn sweeteners, natural and synthetic gums, such as acacia, tragacanth or sodium alginate, carboxymethyl cellulose and polyethylene glycol. Examples of suitable lubrîcants include sodium oleate, sodium stéarate, magnésium stéarate, sodium benzoate, sodium acetate, sodium chloride and the like. Preservatives, stabilizers, dyes and even flavouring agents may be provided in the phannaceutical composition. Examples of preservatives include sodium benzoate, sorbic acid, cysteîne and esters of p-hydroxybenzoic acid, for example, în some embodiments the preservative is selected from sodium benzoate, sorbic acid and esters of p-hydroxybenzoic acid.

Antioxidants and suspending agents may be also used. A further example of a suitable carrier is saccharose. A further example of a preservative is cysteine.

The compositions of the invention may be fonnulated as a food product. For exampie, a food product may provide nutritional benefit in addition to the therapeutic effect of the invention, such as in a nutritional supplément. Similarly, a food product may be fonnulated to enhance the taste of the composition of the invention or to make the composition more attractive to consume by being more similar to a common food item, rather than to a phannaceutical composition. In certain embodiments, the composition of the invention is fonnulated as a milk-based product. The tenu milk-based product means any liquid or semi-solid milk- or whey-based product having a varying fat content. The milk-based product can be, e.g., cow’s milk, goat's milk, sheep's milk, skimmed milk, whole milk, milk recombined from powdered milk and whey without any processîng, or a processed product, such as yoghurt, curdled milk, curd, sour milk, sour whole milk, butter milk and other sour milk products. Another important group includes milk beverages, such as whey beverages, fennented milks, condensed milks, infant or baby milks, flavoured milks, ice cream, miik-containing food such as sweets.

In some embodiments, the compositions of the invention comprise one or more bacterial strains of the genus Blautia and do not contain bacteria from any other genus or comprise only de minimis or bîologically irrelevant amounts of bacteria from another genus.

In certain embodiments, the compositions of the invention contain a single bacterial species and do not contain any other bacterial species. In certain embodiments, the compositions of the invention contain a single bacterial strain and do not contain any other bacterial strains. For example, the compositions of the invention may comprise bacteria only of the species Blautia hydrogenotrophica. Such compositions may comprise only de minimis or bîologically irrelevant amounts of other bacterial strains or species. Such compositions may be a culture that is substantially free from other species of organism. In some embodiments, such compositions may be a lyophilîsate that is substantially free from other species of organism.

In some embodiments, the composition does not comprise bacteria of the species Clostridium and/or does not comprise bacteria of the species Blautiaproducta.

In certain embodiments, the compositions of the invention comprise one or more bacterial strains or bacterial species of the genus Blautia, for example, Blautia hydrogenotrophica, and do not contain any other bacterial genus, or which comprise only de minimis or bîologically irrelevant amounts of bacteria from another genus.

In some embodiments, the compositions of the invention comprise more than one bacterial strain or species. For example, in some embodiments, the compositions of the invention comprise more than one strain from within the same species (e.g. more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40 or 45 strains), and, optionally, do not contain bacteria from any other species. In some embodiments, the compositions of the invention comprise less than 50 strains from within the same species (e.g. less than 45, 40, 35, 30, 25, 20, 15, 12, 10, 9, 8, 7, 6, 5, 4 or 3 strains), and, optionally, do not contain bacteria from any other species. In some embodiments, the compositions ofthe invention comprise 1-40, 1-30, 1-20, 1-19, 1-18, 1-15, 1-10, 1-9, 1-8, 17, 1-6, 1-5, 1-4, 1-3, 1-2, 2-50, 2-40, 2-30, 2-20, 2-15, 2-10, 2-5, 6-30, 6-15, 16-25, or 31-50 strains from within the same species and, optionally, do not contain bacteria from any other species. In some embodiments, the compositions of the invention comprise more than one species from within the same genus (e.g. more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 17, 20, 23, 25, 30, 35 or 40 species), and, optionally, do not contain bacteria from any other genus. In some embodiments, the compositions of the invention comprise less than 50 species from within the same genus (e.g. less than 50, 45, 40, 35, 30, 25, 20, 15, 12, 10, 8, 7, 6, 5, 4 or 3 species), and, optionally, do not contain bacteria from any other genus. In some embodiments, the compositions of the invention comprise 1-50, 1-40, 1-30, 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 15, 1-4, 1-3, 1-2, 2-50, 2-40, 2-30, 2-20, 2-15, 2-10, 2-5, 6-30, 6-15, 16-25, or 31-50 species from within the same genus and, optionally, do not contain bacteria from any other genus. The invention comprises any combination of the foregoîng.

In some embodiments, the composition comprises a microbial consortium. For example, in some embodiments, the composition comprises the Blautia bacterial strain as part of a microbial consortium. For example, in some embodiments, the Blautia bacterial strain is présent in combination with one or more (e.g. at least 2, 3, 4, 5, 10, 15 or 20) other bacterial strains from the genus Blautia and/or other généra with which it can lîve symbiotically in vivo in the intestine. For example, in some embodiments, the composition comprises a bacterial strain of Blautia hydrogenotrophica in combination with a bacterial strain from a different genus. In another example, the composition comprises a bacterial strain of Blautia hydrogenotrophica in combination with a bacterial strain from the genus Blautia or the composition comprises a bacterial strain of Blautia hydrogenotrophica in combination with a bacterial strain from the genus Blautia and a bacterial strain from a different genus. In some embodiments, the microbial consortium comprises two or more bacterial strains obtained from a faeces sample of a single organism, e.g. a human. In some embodiments, the microbial consortium is not found together in nature. For example, in some embodiments, the microbial consortium comprises bacterial strains obtained from faeces samples of at least two different organisms. In some embodiments, the two different organisms are from the same species, e.g. two different humans. In some embodiments, the two different organisms are an infant human and an adult human. In some embodiments, the two different organisms are a human and a non-human mammal.

In some embodiments, the composition comprises the Blautia bacterial strain as part of a microbial consortium which contains fewer than 5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100 or 200 bacterial species. The bacterial species may be from the genus Blautia and/or from other généra with which it can live symbiotically in vivo in the intestine. Those skilled in the art wiil recognise that a bacterial population comprising 200 or fewer different species is signîficantly less complex and more controlled than material derived from a faecal sample which will contam many thousands of different species of bacteria. In preferred embodiments, the composition is not a faecal sample, such as a human faecal sample.

In preferred embodiments, the composition may be formulated as part of a microbial consortium which contains fewer than 10, 11, 12, 13, 14, 15, 16, 17, 28, 19, 20, 30, 40 or 50 bacterial strains. The bacterial strains may be from the genus Blautia and/or from other généra with which it can live symbiotically in vivo in the intestine. In some embodiments, the microbial consortium contains fewer than 30 bacterial strains. In some embodiments, the microbial consortium contains fewer than 20 bacterial strains. In some embodiments, the microbial consortium contains fewer than 10 bacterial strains.In some embodiments, the composition of the invention additionally comprises a bacterial strain that has the same safety and therapeutic effîcacy characteristics as the Blautia hydrogenotrophica strain deposited under accession number DSM 14294, but which is not the Blautia hydrogenotrophica strain deposited under accession number DSM 14294, or which is not a Blautia hydrogenotrophica or which is not a Blautia.

In some embodiments in which the composition of the invention comprises more than one bacterial strain, species or genus, the individual bacterial strains, species or généra may be for separate, sîmultaneous or sequential administration. For example, the composition may comprise ail of the more than one bacterial strain, species or généra, or the bacterial strains, species or généra may be stored separately and be administered separately, simultaneously or sequentially. In some embodiments, the more than one bacterial strains, species or généra are stored separately but are mîxed together prior to use.

In some embodiments, the bacterial strain for use in the invention is obtained from human adult faeces. In some embodiments in which the composition of the invention comprises more than one bacterial strain, ail of the bacterial strains are obtained from human adult faeces or if other bacterial strains are présent, they are présent only in de minimis amounts. The bacteria may hâve been cultured subséquent to being obtained from the human adult faeces and being used in a composition of the invention.

In some embodiments, the one or more Blautia bacterial strains is/are the only therapeutically active agent(s) in a composition of the invention. In some embodiments, the bacterial strain(s) in the composition is/are the only therapeutically active agent(s) in a composition of the invention.

The compositions for use in accordance with the invention may or may not require marketing approval.

In certain embodiments, the invention provides the above pharmaceutical composition, wherein saîd bacterial strain is lyophilised. In certain embodiments, the invention provides the above pharmaceutical composition, wherein said bacterial strain is spray dried. In certain embodiments, the invention provides the above pharmaceutical composition, wherein the bacterial strain is lyophilised or spray dried and wherein it is live. In certain embodiments, the invention provides the above pharmaceutical composition, wherein the bacterial strain is lyophilised or spray dried and wherein it is viable. In certain embodiments, the invention provides the above pharmaceutical composition, wherein the bacterial strain is lyophilised or spray dried and wherein it is capable of partially or totally colonising the intestine. In certain embodiments, the invention provides the above pharmaceutical composition, wherein the bacterial strain is lyophilised or spray dried and wherein it is viable and capable of partially or totally colonising the intestine.

In some cases, the lyophilised or spray dried bacterial strain is reconstituted prior to administration. In some cases, the reconstitution is by use of a diluent described herein.

The compositions of the invention can comprise pharmaceutically acceptable excipients, diluents or carriers.

In certain embodiments, the invention provides a pharmaceutical composition comprising: a bacterial strain as discussed earlier; and a pharmaceutically acceptable excipient, carrier or diluent; wherein the bacterial strain is in an amount sufficient to treat a disorder when administered to a subject in need thereof; and wherein the disorder is sensory hypersensitivity, such as sensory hypersensitivity associated with neuropathy, complex régional pain syndrome, postherpetic neuralgia, fibromyalgia, or migraine. Preferably, the disorder is fibromyalgia. The disorder may be allodynia and/or hyperalgesia, such as allodynia and/or hyperalgesia associated with neuropathy, complex régional pain syndrome, postherpetic neuralgîa, tibromyalgia, or migraine. Preferably, the disorder is tibromyalgia.

In certain embodiments, the invention provides the above phannaceutical composition, wherein the amount of the bacterial strain is from about 1 χ 10³ to about 1 χ 10¹¹ colony forming units per gram with respect to a weight of the composition.

In certain embodiments, the invention provides the above phannaceutical composition, wherein the composition is adminisiered at a dose of 1 g, 3 g, 5 g or 10 g.

In certain embodiments, the invention provides the above phannaceutical composition, wherein the composition is adminisiered by a method selected from the group consisting of oral, rectal, subcutaneous, nasal, buccal, and sublingual.

In certain embodiments, the invention provides the above phannaceutical composition, comprising a carrier selected from the group consisting of lactose, starch, glucose, methyl cellulose, magnésium stéarate, mannitol and sorbitol.

In certain embodiments, the invention provides the above phannaceutical composition, comprising a diluent selected from the group consisting of éthanol, glycerol and water.

In certain embodiments, the invention provides the above phannaceutical composition, comprising an excipient selected from the group consisting of starch, gelatin, glucose, anhydrous lactose, free-flow lactose, beta-lactose, corn sweetener, acacia, tragacanth, sodium alginate, carboxymethyl cellulose, polyethylene glycol, sodium oleate, sodium stéarate, magnésium stéarate, sodium benzoate, sodium acetate and sodium chloride.

In certain embodiments, the invention provides the above phannaceutical composition, further comprising at least one of a preservative, an antioxidant and a stabilizer.

In certain embodiments, the invention provides the above phannaceutical composition, comprising a preservative selected from the group consisting of sodium benzoate, sorbic acid and esters of p-hydroxybenzoic acid.

In certain embodiments, the invention provides the above phannaceutical composition, wherein said bacterial strain is lyophilised.

In certain embodiments, the invention provides the above phannaceutical composition, wherein when the composition is stored in a sealed container at about 4°C or about 25°C and the container is placed in an atmosphère having 50% relative humidity, at least 80% of the bacterial strain as measured in colony forming units, remains after a period of at least about: 1 month, 3 months, 6 months, 1 year, 1.5 years, 2 years, 2.5 years or 3 years.

In some embodiments, the composition of the invention is provided in a sealed container comprising a composition as described herein. In some embodiments, the sealed container is a sachet or bottle. In some embodiments, the composition of the invention is provided in a syringe comprising a composition as described herein.

The composition of the présent invention may, in some embodiments, be provided as a pharmaceutical formulation. For example, the composition may be provided as a tablet or capsule. In some embodiments, the capsule is a gélatine capsule (“gel-cap”). The capsule can be a hard or a soft capsule. In some embodiments, the formulation is a soft capsule. Soft capsules are capsules which may, owing to additions of softeners, such as, for example, glycerol, sorbitol, maltitol and polyethylene glycols, présent in the capsule shell, hâve a certain elasticity and softness. Soft capsules can be produced, for example, on the basis of gélatine or starch. Gelatinebased soft capsules are commercially available from various suppliers. Depending on the method of administration, such as, for example, orally or rectally, soft capsules can hâve various shapes, they can be, for example, round, oval, oblong or torpedo-shaped. Soft capsules can be produced by conventional processes, such as, for example, by the Scherer process, the Accogel process or the droplet or blowing process.

In some embodiments, the compositions of the invention are administered orally. Oral administration may involve swallowîng, so that the compound enters the gastrointestinal tract.

Pharmaceutical formulations suitable for oral administration include solid plugs, solid microparticulates, semî-soiîd and liquid (including multiple phases or dispersed Systems) such as tablets; soft or hard capsules containing mufti- or nano-particulates, liquids (e.g. aqueous solutions), émulsions or powders; lozenges (including liquid-filled); chews; gels; fast dispersing dosage forms; films; ovules; sprays; and buccal/mucoadhesîve patches.

In some embodiments the pharmaceutical formulation is an enteric formulation, i.e. a gastrorésistant formulation (for example, résistant to gastric pH) that is suitable for delivery of the composition of the invention to the intestine by oral administration. Enteric formulations may be parti cul arl y useful when the bacterîa or another component of the composition is acidsensitive, e.g. prone to dégradation under gastric conditions.

In some embodiments, the enteric formulation comprises an enteric coating. In some embodiments, the formulation is an enteric-coated dosage form. For example, the formulation may be an enteric-coated tablet or an enteric-coated capsule, or the like. The enteric coating may be a conventional enteric coating, for example, a conventional coating for a tablet, capsule, or the like for oral delivery. The formulation may comprise a film coating, for ex ample, a thin film layer of an enteric polymer, e.g. an acid-insoluble polymer.

In some embodiments, the enteric formulation is intrinsically enteric, for example, gastrorésistant without the need for an enteric coating. Thus, in some embodiments, the formulation is an enteric formulation that does not comprise an enteric coating. In some embodiments, the formulation is a capsule made from a thermogelling material. In some embodiments, the thermogelling material is a cellulosic material, such as methylcellulose, hydroxymethylcellulose or hydroxypropylmethylcellulose (HPMC). In some embodiments, the capsule comprises a shell that does not contain any film forming polymer. In some embodiments, the capsule comprises a shell and the shell comprises h ydroxypropylm ethyl cellulose and does not comprise any film forming polymer (e.g. see [34]). In some embodiments, the formulation is an intrinsically enteric capsule (for example, Vcaps® from Capsugel).

Culturing methods

The bacterial strains for use in the présent invention can be cultured using standard microbiology techniques as detailed in, for example, référencés [35-37].

The solid or liquid medium used for culture may for example be YCFA agar or YCFA medium. YCFA medium may include (per 100ml, approximate values): Casitone (1.0 g), yeast extract (0.25 g), NaHCOj (0.4 g), cysteine (0.1 g), K₂HPO₄ (0.045 g), KH₂PO₄ (0.045 g), NaCl (0.09 g), (NH₄)₂SO₄ (0.09 g), MgSO₄ 7H₂O (0.009 g), CaCl₂ (0.009 g), resazurin (0.1 mg), hemin (1 mg), biotin (1 pg), cobalamin (1 pg), /j-aminobenzoic acid (3 pg), folie acid (5 pg), and pyridoxamine (15 pg).

General

The practice of the présent invention will employ, unless otherwise indicated, conventional methods of chemistry, biochemistry, molecular biology, immunology and pharmacoiogy, within the skih of the art. Such techniques are explained fully in the literature. See, e.g., references [3845], etc.

The term “comprising” encompasses “including” as well as “consisting” e.g. a composition “comprising” X may consist exclusively of X or may include something additional e.g. X + Y.

The term “about” in relation to anumerical value λ is optional and means, for example, x+10%.

The word “substantially” does not exclude “completely” e.g. a composition which is “substantially free” from Y may be completely free from Y. Where necessary, the word “substantially” may be omitted from the définition of the invention.

References to a percentage sequence identity between two nucléotide sequences means that, 5 when aligned, that percentage of nucléotides are the same in comparing the two sequences. This alignment and the percent homology or sequence identity can be determined using software programs known in the art, for example those described in section 7.7.18 of ref. [46]. A preferred alignment is determined by the Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 5 or 12 (most preferabiy 12) and a gap extension penalty of 2, 10 BLOSUM matrix of 62. The Smith-Waterman homology search algorithm is disclosed in ref. [47].

Unless specifically stated, a process or method comprising numerous steps may comprise additional steps at the beginning or end of the method, or may comprise additional intervenîng steps. Also, steps may be combined, omitted or performed in an alternative order, if appropriate.

Various embodiments of the invention are described herein. It will be appreciated that the features specified in each embodiment may be combined with other specified features, to provide further embodiments. In particular, embodiments highlighted herein as being suitable, typîcal or preferred may be combined with each other (except when they are mutually exclusive).

Ail patent and literature references cited în the présent spécification are hereby incorporated by 20 référencé in their entîrety.

Any référencé to a method for treatment comprising administering an agent to a patient, also covers that agent for use in said method for treatment, as well as the use of the agent in said method for treatment, and the use of the agent in the manufacture of a médicament.

The following examples are offered for illustrative purposes only, and are not intended to limît 25 the scope of the présent invention in any way.

MODES FOR CARRYING OUT THE INVENTION

Exemple 1 - Evaluation of two test compound in an acid-saline rat model of fibromyalgia

Summary

Using the acid-saline rat model of fibromyalgia, the animais received either a composition 30 comprising Blautia or one of several contrais. The compositions of the invention were found inter alla to reduce mechanical allodynia in this rat model, indicating a réduction in fibromyalgia.

Animal model

The experiments used the acid-saline rat model of fibromyalgia using male Sprague-Dawley SD rats (n = 12/group). In this model, non-inflammatory pain is induced by repeated injections of 5 acid saline (pH 4.0) separated by 5 days. To this end, rats were anesthetized with isoflurane (24%) prior to injection of 100 pL of pH 4.0 saline into the left gastrocnemius muscle. Five days later, the process was repeated; hyperalgesia develops within several hours of the 2^nd injection. Model induction was performed for ali treatment groups with the exception of Normal Control rats, who underwent a sham injection procedure (pH 7.2 saline) and received an équivalent volume of vehicle (i.e. phosphate buffered saline; PBS) delivered in an identical manner to that used for the test article (i.e. daily oral gavage).

Study design

Animais were acclimated to the facility and expérimenter handling for a minimum of 7 days, during which time rats received the initial exposure to sucrose water to prevent later neophobic effects and allow for assessment of baseline water consumption. At this time, rats were randomly assigned to treatment groups based on body weight as foliows:

Group	Model Induction	Treatment	Purpose	# of Animais
A	100 pL saline pH 4.0	Blautia hydrogenotrophica (p.o) + Saline (s.c)	Experimental	12
B	100 pL saline pH 4.0	Lyobuffer (p.o) + Saline (s.c)	Experimental	12
C	100 pL saline pH 7.2	PBS (p.o) + Saline (s.c)	Normal Control	12
D	100 pL saline pH 4.0	PBS (p.o) + Saline (s.c)	Disease Control	12
E	100 pL saline pH 4.0	PBS (p.o) + Buprénorphine in Saline (s.c)	Positive Control	12

On the final day of acclimation, blood and faecal samples were obtained.

Following the acclimation phase, daily oral gavage administration of the appropriate test article or vehicle commenced according to assigned groups (see table above). Daily administration continued throughout the remainder of the study.

During the second treatment week, évaluation of mechanical hyperalgesia (i.e. Von Frey mono filament assessment) was performed to pro vide a baseline measure. During this week, preinduction sucrose consumption was also measured in préparation for later anhedonia testing. Blood and faecal samples were obtained at the conclusion of the two full weeks of treatment.

Mode! induction began at the third week of treatment. A cage side pain assessment was performed 2x per day for the first week following model induction, and then Ix per day for the remainder of the study. Mechanical hyperalgesia was evaluated at 24- and 72-hours postinduction, and again at 1 and 2 weeks, while somatosensory hind-paw placements, functional movement assessments, and anhedonia testing were performed weekly. At the conclusion of behavioural testing, a final set of blood and faecal samples was obtained the day before euthanasia.

On the day of euthanasia, tissues were harvested and prepared for subséquent analysis.

Strain

Blautia hydrogenotrophica (BH) strain DSM 14294.

Weight

Rats were weighed 24 hours after arrivai in the facility, and a minimum of Ix per week thereafter. Figure 1 shows no différence in weight between the groups at the initiation of the study (Normal Control: 206.80 ± 9.10g; Disease Control: 206.70 ± 6.54g; Blautia hydrogenotrophica·. 204.50 ± 10.33g; Lyobuffer: 206.80 ± 9.31g). While most rats lost some weight at 24-hours post-induction, this loss did not differ between groups and ail rats continued to gain weight through the following weeks. By the end of the experiment a trend was observed that the Blautia hydrogenotrophica treated and normal control animais gained more weight compared to the disease control and Lyobuffer treated animais.

Pain

Pain scores were assigned 2x a day for the first post-induction week, and then Ix per day for the duration of the study. S coring is performed cage side using a 4-poînt rat grimace scale [48]. Evaluations include the presence/absence of orbital tightening and nose/cheek flattening, as well as positioning of ears and whiskers.

Sensorimotor Function

Tactile hind-paw placement allows for assessment of sensorimotor intégration in response to tactile and proprioceptive stimuli. Scoring was perfonned once per week following model induction, for a total of 2 sessions. To perforai the test, rats are held in the expérimenter’s hand with limbs hangîng freely, and the body held at a 45° angle to a table edge. The animal is brought upwards toward the surface of the table, until the dorsal portion of the hind-paw touches the table. A normal response is to immediately place the paw on the table. The day’s score is recorded as a mean of 5 trials.

Figure 2 shows that surprisingly Blautia hydrogenotrophica treated rats showed improved perfonnance in Week 2, a phenomenon that was not présent in any other group. In the rîght (ipsilateral to injection) paw, this improvement reached statistical significance compared to both Normal Control and Lyobuffer Groups (p = 0.048 and p = 0.017, respectively; T-Test), and trended toward a différence from Disease Control (p = 0.119; T-Test).

Also, interestingly, a différence was found between the ipsilateral vs. contralatéral paw placements within groups. This évaluation indicated that Normal Control rats placed less effectively on the side ipsilateral to injection, a différence that trended toward statistical significance by Week 2 (p = 0.054; paired T-Test). A decrease in placing in the ipsilateral paw compared to contralatéral was also noted in the Lyobuffer Group, a différence that was statistically significance in both Week I and Week 2 (p = 0.020 for each; paired T-Test). However, no within group différence in placing was seen for either Disease Control or the Blautia hydrogenotrophica treated rats, although it is important to note that the Disease Control rats appeared to hâve équivalent difficulty with both ipsilateral and contralatéral placing at both time points, whîle the Blautia hydrogenotrophica treated rats showed improved (non-statîstîcally significant) performance for both paws in Week 2.

Functional Movement

Hind-limb function is scored in an open arena using a modified version of the 21-point Basso, Beatties, Bresnahan (BBB) Locomotor Rating Scale [49], with assessments performed once per week following model induction, for a total of 2 sessions. Evaluation includes paw placement, stability, toe positioning, limping, and weight support (active and statîonary).

Anhedonia (Sucrose Preference)

Prior to model induction and test article administration, rats were acclimated to sucrose sweetened water, and a baseline level for water consomption were established over a 24-hour period. Following this initial exposure, sucrose preference testing was performed the week pnor to model induction, and then once per week after the model is induced. For testing, regular water bottles were replaced with two pre-weighed bottles, one containing regular water, and one with a 1% sucrose solution. After 24-hours, bottles were weighed again, and consumption of each was recorded. A decrease in consumption of a rewarding treat (sucrose water) over a 24-hour présentation period is considered indicative of depressed behaviour (anhedonia). No différences between groups was noted for sucrose consumption.

Mechanical Allodynia - Von Frey Monofilament Testing

Testing for mechanical allodynia was performed using Von Frey monofilaments, and scored via the Dixon Up-Down method to provide a 50% paw withdrawal threshold. Prior to model induction, no statistically significant différence was noted between assigned groups.

Testing was performed at baseline (i.e. prior to model induction), 24 hours post-induction, and again at 72-hours, 1 week, and 2 weeks for a total of 5 sessions. The testing apparatus consists of a small chamber with a wire mesh (5mm square openings) flooring. The apparatus is elevated to allow for easy monofilament application to the plantar surface of each rat paw. Animais are allowed to acclimate to the testing apparatus for 30-minutes prior to each day’s test run. Monofilament testing range for rat is 3.61 - 5.18 (0.41 - 15.1g bending force). Testing begins with a 2-second application of the 4.56 (mid-range) monofilament, perpendicular to the plantar région of the ipsilateral hind-paw, and with enough pressure to ensure the monofilament fibre bends. Rats are observed during monofilament application, and for 2-seconds following. A positive response is a rapid withdrawal of the hind-paw and may include shaking or licking of the paw. If the response is ambiguous, the same monofilament is re-applied after a 30-second delay. If the response is positive, the next lightest monofilament is assessed, while a négative response is followed by application of the next heavier monofilament. Time between applications is 10-seconds (with the exception of an ambiguous response as outlined above). Six readîngs are obtained for analysis. Data analysis is via the up-down method [50]. Statistically significant différences from Normal Control are îndicated by the asterisk.

Figure 3 shows the results of the Von Frey monofilament assessment. Administration of compositions comprising Blautia hydrogenotrophica led to a notable réduction in mechanical allodynia compared to the control groups.

Muscle Hyperalgesia

Mechanical nociceptive threshold in the gastrocnemius muscle was quantified at two-weeks post-induction using a digital compression gauge applied to the ipsilateral gastrocnemius muscle until withdrawal of the limb occurred. Three consecutive trials were performed and averaged. The compression force applied at the time of withdrawal was recorded as the compression withdrawal threshold.

As depicted in Figure 4, there was no main effect for this test at this time point. Overall, rats were less responsive than expected during testing, with compression scores to withdrawal 200 to 400g higher on average than during the Pilot Study. It should be noted that, although there were no between groups différences in this test, the Blautia hydrogenotrophica treated rats performed equivalently to Positive Control animais.

Collection of Blood at Termination

In addition to in-life blood draws described above, a final cardiac blood collection was performed at euthanasia while rats were under anaesthesia. Préparation of plasma samples was identical to that described above [i.e. both EDTA and lithium-heparin plasma), with samples stored at -80°C.

Collection of Dorsal Root Ganglion at Termination

At the conclusion of the in vivo portion of the study, rats were deeply anesthetized with isoflurane, intestinal samples were collected, and dorsal root ganglion (DRG) was dissected out. Following tissue harvest, animais were euthanized via décapitation.

DRG was dissected out, submersion fixed in 10% neutral buffered formalin (NB F), cryoprotected in a 30% w/v sucrose solution, frozen and embedded in OCT media, and stored at -80°C. Three 10pm thick sections per DRG/animal were eut using a cryostat (-21°C), and immunohistochemistry IHC analysis was performed on DRG sections from S rats in each treatment group using validâted markers for TNF-α and GFAP.

Collection of Gut Tissue at Termination

Approximately 24 hours after the final administration of test article, rats were deeply anesthetized with isoflurane and the following organs were harvested as quickly as possible:

• The ileum was excised 0.5 cm upstream of the caecum, eut longitudinal!y, rinsed (flushed with saline solution), and the fat and the contents were removed carefully. Three equal pièces of 1.0 cm each were collected:

Proximal sample were placed in RNALater™, Middle sample were snap-frozen in liquid nitrogen.

- Distal sample were immersion-fixed in 4% paraformaldéhyde (PFA), cryoprotected in graded sucrose solution (15-30%) and embedded in OCT and frozen.

• The caecum was excised whole with its contents and snap-frozen in liquid nitrogen.

• The colon was excised 0.5 cm downstream of the caecum, eut longitudînally, rinsed (flushed with saline solution), and the fat and the contents were removed carefiilly. Three equal pièces of 1.0 cm each of the ascending colon were collected:

Proximal sample was placed in RNA Later™.

Middle sample was snap-frozen in liquid nitrogen.

Distal sample was immersion-fixed in 4% paraformaldéhyde (PFA), cryoprotected in graded sucrose solution (15-30%), embedded in OCT and frozen.

• Transverse colon was collected whole, eut longitudînally, rinsed (flushed with saline solution) to remove contents, and snap-frozen in liquid nitrogen.

• Descending colon was collected whole, eut longitudînally, rinsed (flushed with saline solution) to remove contents, and snap-frozen in liquid nitrogen.

Additional Measures

Two additional measures related to animai welfare were evaluated during this study. Pain was scored cage-side using a 4-point grimace scale 2x per day for the first post-induction week, and then Ix per day for the duration of the study, while functional movement was assessed via a modified Locomotor Rating Scale with assessments performed once per week following model induction for a total of 2 sessions. No déficits were noted in eîther of these measures, with ail animais exhibiting no overt signs of unelîcited pain or distress at any time point. Table 2 provides these data.

Table 2: Measures of Animal Welfare/Model Parameters

Test	Normal Control	Disease Control	Blautia hydrogenotrophica	Lyobuffer
Pain Assessment	0	0	0	0
Functional Movement	7	7	7	7

Conclusions

The results from this study support the conclusion that the oral administration of Blautia hydrogenotrophica has bénéficiai effects on several factors conducive to promoting a more positive outcome in the acid-saline model of fibromyalgia. Lyobuffer treatment did not offer any protection, consistently resulting in performance no better than Disease Control levels. It is important to note that, while différences seen in Blautia hydrogenotrophica treated animais did not achieve statistical significance compared to Disease Control, this does not preclude their biological significance, especially since this model is by nature înherently variable.

Several results support the conclusion from this study. First, Normal Control and Blautia hydrogenotrophica treated rats showed a trend toward an increased weight gain following model induction compared to Disease Control and Lyobuffer Groups.

In behavioural tests, Blautia hydrogenotrophica treated rats perfomied at or better than Normal Control levels, with neither of these Groups exhibiting a statistically significant différence from the Positive Control. Additionally, somato sensory testing indicated that Blautia hydrogenotrophica treatment appeared to improve performance by Week 2 post-induction, an achievement not noted in any other group.

The lack of statistical différences between Normal Control and Disease Control Groups, while not anticipated based on earlîer pilot work, may be a conséquence of the increased handlîng required throughout this project. Daily administration of experimental compounds via oral gavage before model induction and continuing throughout the remaining weeks of the study, as well as repeated blood draws, required animais to be handled and restrained regularly, often multiple times per day. In addition, the behavioural testing schedule necessitated repeated handlîng above what occurred during the shorter, more sîmplified pilot study. Reports in human literature indicate that exercise may be bénéficiai for modulating symptoms of fibromyalgia [51 ]. In rats, exercise also has been shown to attenuate pain response [52]. In the current project, measurable changes were often observed when comparing Disease Control to Positive Control animais. Given these results, it is possible that the model simply lacked the robustness necessary in the 2^nd post-induction week for détection of more subtle alterations.

Sequences

SEQ ID NO:1 (Blautia stercoris strain GAM6-1 16S ribosomal RNA gene, partial sequence HM626177) tgcaagtcga gcgaagcgct tacgacagaa ccttcggggg aagatgtaag ggactgagcg gcggacgggt gagtaacgcg tgggtaacct gcctcataca gggggataac agttggaaac

121 ggctgctaat accgcataag cgcacggtat cgcatgatac agtgtgaaaa actccggtgg

181 tatgagatgg acccgcgtct gattagctag ttggaggggt aacggcccac caaggcgacg

241 atcagtagcc ggcctgagag ggtgaacggc cacattggga ctgagacacg gcccagactc

301 ctacgggagg cagcagtggg gaatattgca caatggggga aaccctgatg cagcgacgcc

361 gcgtgaagga agaagtatct cggtatgtaa acttctatca gcagggaaga aaatgacggt

421 acctgactaa gaagccccgg ctaactacgt gccagcagcc gcggtaatac gtagggggca

481 agcgttatcc ggatttactg ggtgtaaagg gagcgtagac ggaagagcaa gtctgatgtg

541 aaaggctggg gcttaacccc aggactgcat tggaaactgt ttttcttgag tgccggagag

601 gtaagcggaa ttcctagtgt agcggtgaaa tgcgtagata ttaggaggaa caccagtggc

661 gaaggcggct tactggacgg taactgacgt tgaggctcga aagcgtgggg agcaaacagg

721 attagatacc ctggtagtcc acgccgtaaa cgatgaatac taggtgttgg ggagcaaagc

781 tcttcggtgc cgcagcaaac gcaataagta ttccacctgg ggagtacgtt cgcaagaatg

841 aaactcaaag gaattgacgg ggacccgcac aagcggtgga gcatgtggtt taattcgaag

901 caacgcgaag aaccttacca agtcttgaca tcgatctgac cggttcgtaa tggaaccttt

961 ccttcgggac agagaagaca ggtggtgcat ggttgtcgtc agctcgtgtc gtgagatgtt

1021 gggttaagtc ccgcaacgag cgcaacccct atcctcagta gccagcaggt gaagctgggc

1081 actctgtgga gactgccagg gataacctgg aggaaggcgg ggacgacgtc aaatcatcat

1141 gccccttatg atttgggcta cacacgtgct acaatggcgt aaacaaaggg aagcgagccc

1201 gcgaggggga gcaaatccca aaaataacgt cccagttcgg actgcagtct gcaactcgac

1261 tgcacgaagc tggaatcgct agtaatcgcg aatcagaatg tcgcggtgaa

ÎO tacgttcccg

1321 ggtcttgtac acaccgcccg tcacaccatg ggagtcagta acgcccgaag te

SEQ ID NO:2 (Blautia wexlerae strain WAL 14507 16S ribosomal RNA gene, partial sequence EF036467) caagtcgaac gggaattant ttattgaaac ttcggtcgat ttaatttaat tctagtggcg gacgggtgag taacgcgtgg gtaacctgcc ttatacaggg ggataacagt cagaaatggc

121 tgctaatacc gcataagcgc acagagctgc atggctcagt gtgaaaaact ccggtggtat

181 aagatggacc cgcgttggat tagcttgttg gtggggtaac ggcccaccaa ggcgacgatc

241 catagccggc ctgagagggt gaacggccac attgggactg agacacggcc cagactccta

301 cgggaggcag cagtggggaa tattgcacaa tgggggaaac cctgatgcag cgacgccgcg

361 tgaaggaaga agtatctcgg tatgtaaact tctatcagca gggaagatag tgacggtacc

421 tgactaagaa gccccggcta actacgtgcc agcagccgcg gtaatacgta gggggcaagc

481 gttatccgga tttactgggt gtaaagggag cgtagacggt gtggcaagtc tgatgtgaaa

541 ggcatgggct caacctgtgg actgcattgg aaactgtcat acttgagtgc cggaggggta

601 agcggaattc ctagtgtagc ggtgaaatgc gtagatatta ggaggaacac cagtggcgaa

661 ggcggcttac tggacggtaa ctgacgttga ggctcgaaag cgtggggagc aaacaggatt

721 agataccctg gtagtccacg ccgtaaacga tgaataacta ggtgtcgggt ggcaaagcca

781 ttcggtgccg tcgcaaacgc agtaagtatt ccacctgggg agtacgttcg caagaatgaa

841 actcaaagga attgacgggg acccgcacaa gcggtggagc atgtggttta attcgaagca

901 acgcgaagaa ccttaccaag tcttgacatc cgcctgaccg atccttaacc ggatctttcc

961 ttcgggacag gcgagacagg tggtgcatgg ttgtcgtcag ctcgtgtcgt gagatgttgg

1021 gttaagtccc gcaacgagcg caacccctat cctcagtagc cagcatttaa ggtgggcact

1081 ctggggagac tgccagggat aacctggagg aaggcgggga tgacgtcaaa tcatcatgcc

1141 ccttatgatt tgggctacac acgtgctaca atggcgtaaa caaagggaag cgagattgtg

1201 agatggagca aatcccaaaa ataacgtccc agttcggact gtagtctgca acccgactac

1261 acgaagctgg aatcgctagt aatcgcggat cagaatgccg cggtgaatac gttcccgggt

1321 cttgtacaca ccgcccgtca caccatggga gtcagtaacg cccgaagtca gtgacctaac

1381 tgcaaagaag gagctgccga aggcgggacc gatgactggg gtgaagtcgt aacaaggt

SEQ ID N0:3 (consensus 16S rRNA sequence for Blautia stercoris strain 830)

TTTKGTCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGTCGAGCGAAGCGCTT

ACGACAGAACCTTCGGGGGAAGATGTAAGGGACTGAGCGGCGGACGGGTGAGTAACGCGTGGGT

AACCTGCCTCATACAGGGGGATAACAGTTGGAAACGGCTGCTAATACCGCATAAGCGCACAGTA TCGCATGATACAGTGTGAAAAACTCCGGTGGTATGAGATGGACCCGCGTCTGATTAGCTAGTTG GAGGGGTAACGGCCCACCAAGGCGACGATCAGTAGCCGGCCTGAGAGGGTGAACGGCCACATTG GGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAA ACCCTGATGCAGCGACGCCGCGTGAAGGAAGAAGTATCTCGGTATGTAAACTTCTATCAGCAGG GAAGAAAATGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGTAATA CGTAGGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGAGCGTAGACGGAAGAGCAAGTC TGATGTGAAAGGCTGGGGCTTAACCCCAGGACTGCATTGGAAACTGTTTTTCTTGAGTGCCGGA GAGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCG AAGGCGGCTTACTGGACGGTAACTGACGTTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAG ATACCCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTTGGGGAGCAAAGCTCTTCGGTG CCGCAGCAAACGCAATAAGTATTCCACCTGGGGAGTACGTTCGCAAGAATGAAACTCAAAGGAA TTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTATTCGAAGCAACGCGAAGAACCTTAC CAAGTCTTGACATCGATCTGACCGGTTCGTAATGGAACCTTTCCTTCGGGACAGAGAAGACAGG TGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAAC CCCTATCGTCAGTAGCCAGCAGGTAAAGCTGGGCACTCTGAGGAGACTGCCAGGGATAACCTGG AGGAAGGCGGGGACGACGTCAAATCATCATGCCCCTTATGATTTGGGCTACACACGTGCTACAA TGGCGTAAACAAAGGGAAGCGAGCCCGCGAGGGGGAGCAAATCCCAAAAATAACGTCCCAGTTC GGACTGCAGTCTGCAACTCGACTGCACGAAGCTGGAATCGCTAGTAATCGCGAATCAGAATGTC GCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATGGGAGTCAGTAACGCCC GAAGTCAGTGACCCAACCTTAGGGAGGGAGCTGCCGAAGGCGGGATTGATAACTGGGGTGAAGT CTAGGGGGT

SEQ ID NO:4 (consensus 16S rRNA sequence for Blautia wexlerae straîn NCIMB 42486)

TTCATTGAGACTTCGGTGGATTTAGATTCTATTTCTAGTGGCGGACGGGTGAGTAACGCGTGGG TAACCTGCCTTATACAGGGGGATAACAGTCAGAAATGGCTGCTAATACCGCATAAGCGCACAGA GCTGCATGGCTCAGTGTGAAAAACTCCGGTGGTATAAGATGGACCCGCGTTGGATTAGCTTGTT GGTGGGGTAACGGCCCACCAAGGCGACGATCCATAGCCGGCCTGAGAGGGTGAACGGCCACATT GGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGA AACCCTGATGCAGCGACGCCGCGTGAAGGAAGAAGTATCTCGGTATGTAAACTTCTATCAGCAG GGAAGATAGTGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGTAAT ACGTAGGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGAGCGTAGACGGTGTGGCAAGT CTGATGTGAAAGGCATGGGCTCAACCTGTGGACTGCATTGGAAACTGTCATACTTGAGTGCCGG AGGGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGC

GAAGGCGGCTTACTGGACGGTAACTGACGTTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTA GATACCCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTCNGGGGAGCATGGCTCTTCGG TGCCGTCGCAAACGCAGTAAGTATTCCACCTGGGGAGTACGTTCGCAAGAATGAAACTCAAAGG AATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCT TACCAAGTCTTGACATCCGCCTGACCGATCCTTAACCGGATCTTTCCTTCGGGACAGGCGAGAC AGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGC AACCCCTATCCTCAGTAGCCAGCATTTAAGGTGGGCACTCTGGGGAGACTGCCAGGGATAACCT GGAGGAAGGCGGGGATGACGTCAAATCATCATGCCCCTTATGATTTGGGCTACACACGTGCTAC AATGGCGTAAACAAAGGGAAGCGAGATCGTGAGATGGAGCAAATCCCAAAAATAACGTCCCAGT TCGGACTGTAGTCTGCAACCCGACTACACGAAGCTGGAATCGCTAGTAATCGCGGATCAGAATG CCGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATGGGAGTCAGTAACGC CCGAAGTCAGTGACCTAACTGCAAAGAAGGAGCTGCCGAA

SEQ ID NO:5 (Blautia hydrogenotrophica strain S5a36 16S ribosomal RNA gene, partial sequence - X95624.1) gatgaacgct ggcggcgtgc ttaacacatg caagtcgaac gaagcgatag agaacggaga tttcggttga agttttctat tgactgagtg gcggacgggt gagtaacgcg tgggtaacct

121 gccctataca gggggataac agttagaaat gactgctaat accgcataag cgcacagctt

181 cgcatgaagc ggtgtgaaaa actgaggtgg tataggatgg acccgcgttg gattagctag

241 ttggtgaggt aacggcccac caaggcgacg atccatagcc ggcctgagag ggtgaacggc

301 cacattggga ctgagacacg gcccaaactc ctacgggagg cagcagtggg gaatattgca

361 caatggggga aaccctgatg cagcgacgcc gcgtgaagga agaagtatct cggtatgtaa

421 acttctatca gcagggaaga aagtgacggt acctgactaa gaagccccgg ctaattacgt

481 gccagcagcc gcggtaatac gtaaggggca agcgttatcc ggatttactg ggtgtaaagg

541 gagcgtagac ggtttggcaa gtctgatgtg aaaggcatgg tggactgcat

601 tggaaactgt cagacttgag tgccggagag gcaagcggaa agcggtgaaa

661 tgcgtagata ttaggaggaa caccagtggc gaaggcggcc taactgacgt

721 tgaggctcga aagcgtgggg agcaaacagg attagatacc acgctgtaaa

781 cgatgaatac taggtgtcgg gtggcaaagc cattcggtgc gcaataagta

841 ttcccacctg gggagtacgt tcgcaagaat gaaactcaaa gggacccgca

901 caagcggtgg agcatgtggt ttaattcgaa gcaacgcgaa aaatcttgac

961 atccctctga ccgggaagta atgttccctt ttcttcggaa aggtggtgca

1021 tggttgtcgt cagctcgtgt cgtgagatgt tgggttaagt gcgcaaccct

1081 tattcttagt agccagcagg tagagctggg cactctaggg ggataacctg

1141 gaggaaggtg gggatgacgt caaatcatca tgccccttat acacacgtgc

1201 tacaatggcg taaacaaagg gaagcgaagg ggtgacctgg aaaaataacg

1261 tctcagttcg gattgtagtc tgcaactcga ctacatgaag tagtaatcgc

1321 gaatcagaat gtcgcggtga atacgttccc gggtcttgta gtcacaccat

1381 gggagtcagt aacgcccgaa gtcagtgacc caaccnaaag ccgaaggtgg

1441 gactgataac tggggtga gctcaacctg ttcctagtgt tgctggacgg ctggtagtcc cgcagcaaac ggaattgacg gaaccttacc cagaggagac cccgcaacga agactgccag gatttgggct agcaaatctc ctggaatcgc cacaccgccc gagggagctg

SEQ ID NO:6 {Blautia producta sîrain NCIMB 43170 16S rRNA gene sequence - consensus)

GACTTCGGGCGTTACTGACTCCCATGGTGTGACGGGCGGTGTGTACAAGACCCGGGAACGTATT CACCGCGGCATTCTGATCCGCGATTACTAGCGATTCCAGCTTCGTGCAGTCGAGTTGCAGACTG CAGTCCGAACTGGGACGTTATTTTTGGGATTCGCTCAACATCGCTGTCTCGCTTCCCTTTGTTT ACGCCATTGTAGCACGTGTGTAGCCCAAATCATAAGGGGCATGATGATTTGACGTCGTCCCCGC 5 CTTCCTCCGGGTTATCCCCGGCAGTCTCCCTAGAGTGCCCACCATCATGTGCTGGCTACTAAGG

ATAAGGGTTGCGCTCGTTGCGGGACTTAACCCAACATCTCACGACACGAGCTGACGACAACCAT GCACCACCTGTCTCCTCTGCCCCGAAGGGAAGTCCCCGTTACGGGACGGTCAGAGGGATGTCAA GACTTGGTAAGGTTCTTCGCGTTGCTTCGAATTAAACCACATGCTCCACCGCTTGTGCGGGTCC CCGTCAATTCCTTTGAGTTTCATTCTTGCGAACGTACTCCCCAGGTGGAATACTTATTGCGTTT 10 GCTGCGGCACCGAATGGCTTTGCCACCCGACACCTAGTATTCATCGTTTACGGCGTGGACTACC

AGGGTATCTAATCCTGTTTGCTCCCCACGCTTTCGAGCCTCAACGTCAGTTACCGTCCAGTAAG CCGCCTTCGCCACTGGTGTTCCTCCTAATATCTACGCATTTCACCGCTACACTAGGAATTCCGC TTACCTCTCCGGCACTCTAGAACAACAGTTTCCAATGCAGTCCTGGGGTTAAGCCCCAGCCTTT CACATCAGACTTGCTCTTCCGTCTACGCTCCCTTTACACCCAGTAAATCCGGATAACGCTTGCC 15 CCCTACGTATTACCGCGGCTGCTGGCACGTAGTTAGCCGGGGCTTCTTAGTCAGGTACCGTCAT

TTTCTTCCCTGCTGATAGAAGTTTACATACCGAGATACTTCTTCCTTCACGCGGCGTCGCTGCA TCAGGGTTTCCCCCATTGTGCAATATTCCCCACTGCTGCCTCCCGTAGGAGTCTGGGCCGTGTC TCAGTCCCAATGTGGCCGTTCACCCTCTCAGGCCGGCTACTGATCGTCGCCTTGGTGGGCCGTT ACCCCTCCAACTAGCTAATCAGACGCGGGTCCATCTCATACCACCGGAGTTTTTCACACCAGAC

CATGCGGTCCTGTGCGCTTATGCGGTATTAGCAGTCATTTCTAACTGTTATCCCCCTGTATGAG

GCAGGTTACCCACGCGTTACTCACCCGTCCGCCGCTCAGTCACAAAGACTTCAATCCGAAGAAA TCCTGTCTTAGTGCTTCGCT

SEQ ID NO:7 - Blautia coccoides strain 16S rRNA gene sequence -Contig 15 consensus 25 sequence 2 reads assembled using Geneîous

TCGGCAGCTCCTTCCTTTCGGTTAGGTCACTGACTTCGGGCGTTACTGACTCCCATGGTGTGAC GGGCGGTGTGTACAAGACCCGGGAACGTATTCACCGCGGCATTCTGATCCGCGATTACTAGCGA TTCCAGCTTCGTGCAGTCGAGTTGCAGACTGCAGTCCGAACTGGGACGTTATTTTTGGGATTCG CTCAACATCGCTGTCTCGCTTCCCTTTGTTTACGCCATTGTAGCACGTGTGTAGCCCAAATCAT

AAGGGGCATGATGATTTGACGTCGTCCCCGCCTTCCTCCGGGTTATCCCCGGCAGTCTCCCTAG AGTGCCCACCATCATGTGCTGGCTACTAAGGATAAGGGTTGCGCTCGTTGCGGGACTTAACCCA acatctcacgacacgagctgacgacaaccatgcaccacctgtctcctctgccccgaagggaagt CCCCGTTACGGGACGGTCAGAGGGATGTCAAGACTTGGTAAGGTTCTTCGCGTTGCTTCGAATT

AAACCACATGCTCCACCGCTTGTGCGGGTCCCCGTCAATTCCTTTGAGTTTCATTCTTGCGAAC

GTACTCCCCAGGTGGAATACTTATTGCGTTTGCTGCGGCACCGAATGGCTTTGCCACCCGACAC CTAGTATTCATCGTTTACGGCGTGGACTACCAGGGTATCTAATCCTGTTTGCTCCCCACGCTTT CGAGCCTCAACGTCAGTTACCGTCCAGTAAGCCGCCTTCGCCACTGGTGTTCCTCCTAATATCT ACGCATTTCACCGCTACACTAGGAATTCCGCTTACCTCTCCGGCACTCTAGAACAACAGTTTCC AATGCAGTCCTGGGGTTAAGCCCCAGCCTTTCACATCAGACTTGCTCTTCCGTCTACGCTCCCT TTACACCCAGTAAATCCGGATAACGCTTGCCCCCTACGTATTACCGCGGCTGCTGGCACGTAGT TAGCCGGGGCTTCTTAGTCAGGTACCGTCATTTTCTTCCCTGCTGATAGAAGTTTACATACCGA GATACTTCTTCCTTCACGCGGCGTCGCTGCATCAGGGTTTCCCCCATTGTGCAATATTCCCCAC TGCTGCCTCCCGTAGGAGTCTGGGCCGTGTCTCAGTCCCAATGTGGCCGTTCACCCTCTCAGGC CGGCTACTGATCGTCGCCTTGGTGGGCCGTTACCCCTCCAACTAGCTAATCAGACGCGGGTCCA TCTCATACCACCGGAGTTTTTCACACCAGACCATGCGGTCCTGTGCGCTTATGCGGTATTAGCA GTCATTTCTAACTGTTATCCCCCTGTATGAGGCAGGTTACCCACGCGTTACTCACCCGTCCGCC GCTCAGTCACAAAGACTTCAATCCGAAGAAATCCGTCTTAGTGCTTCGCTCGACTGCA

SEQ ID NO:8 - Blautia coccoides strain 16S rRNA gene sequence -Contig consensus sequence 2 reads assembled using Geneious

GGTCGCTTCGGCAGCTCTTCCTTTCGGTTAGGTCAGTGACTTCGGGCGTTACTGACTCCCATGG TGTGACGGGCGGTGTGTACAAGACCCGGGAACGTATTCACCGCGGCATTCTGATCCGCGATTAC TAGCGATTCCAGCTTCGTGCAGTCGAGTTGCAGACTGCAGTCCGAACTGGGACGTTATTTTTGG GATTCGCTCAACATCGCTGTCTCGCTTCCCTTTGTTTACGCCATTGTAGCACGTGTGTAGCCCA AATCATAAGGGGCATGATGATTTGACGTCGTCCCCGCCTTCCTCCGGGTTATCCCCGGCAGTCT CCCTAGAGTGCCCACCATCATGTGCTGGCTACTAAGGATAAGGGTTGCGCTCGTTGCGGGACTT AACCCAACATCTCACGACACGAGCTGACGACAACCATGCACCACCTGTCTCCTCTGCCCCGAAG GGAAGTCCCCGTTACGGGACGGTCAGAGGGATGTCAAGACTTGGTAAGGTTCTTCGCGTTGCTT CGAATTAAACCACATGCTCCACCGCTTGTGCGGGTCCCCGTCAATTCCTTTGAGTTTCATTCTT GCGAACGTACTCCCCAGGTGGAATACTTATTGCGTTTGCTGCGGCACCGAATGGCTTTGCCACC CGACACCTAGTATTCATCGTTTACGGCGTGGACTACCAGGGTATCTAATCCTGTTTGCTCCCCA CGCTTTCGAGCCTCAACGTCAGTTACCGTCCAGTAAGCCGCCTTCGCCACTGGTGTTCCTCCTA ATATCTACGCATTTCACCGCTACACTAGGAATTCCGCTTACCTCTCCGGCACTCTAGAACAACA GTTTCCAATGCAGTCCTGGGGTTAAGCCCCAGCCTTTCACATCAGACTTGCTCTTCCGTCTACG CTCCCTTTACACCCAGTAAATCCGGATAACGCTTGCCCCCTACGTATTACCGCGGCTGCTGGCA CGTAGTTAGCCGGGGCTTCTTAGTCAGGTACCGTCATTTTCTTCCCTGCTGATAGAAGTTTACA TACCGAGATACTTCTTCCTTCACGCGGCGTCGCTGCATCAGGGTTTCCCCCATTGTGCAATATT CCCCACTGCTGCCTCCCGTAGGAGTCTGGGCCGTGTCTCAGTCCCAATGTGGCCGTTCACCCTC

TCAGGCCGGCTACTGATCGTCGCCTTGGTGGGCCGTTACCCCTCCAACTAGCTAATCAGACGCG GGTCCATCTCATACCACCGGAGTTTTTCACACCAGACCATGCGGTCCTGTGCGCTTATGCGGTA TTAGCAGTCATTTCTAACTGTTATCCCCCTGTATGAGGCAGGTTACCCACGCGTTATCACCCGT CCGCCGCTCAGTCACAAAGACTTCAATCCGAAGAAATCCGTCTTAGCGCTCCGCTCGACTGCAT

GGTAGC

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Claims (16)

1. A composition comprising a bacterial strain of the genus Blautia for use in treating or preventing sensory hypersensitivity.

2. A composition comprising a bacterial strain of the genus Blautia for use in treating or preventing allodynia and/or hyperalgesia.

3. The composition for use according to claim 1 or claim 2, wherein the composition is for use in treating or preventing (a) sensory hypersensitivity, and/or (b) allodynia and/or hyperalgesia in a subject dîagnosed with neuropathy, compiex régional pain syndrome, postherpetic neuralgia, fibromyalgia, or migraine.

4. The composition for use according to claim 2, wherein the subject has been diagnosed with fibromyalgia.

5. The composition for use according to any preceding claim, wherein the composition is for use în a patient who has not been diagnosed with viscéral hypersensitivity.

6. The composition for use according to any preceding claim, wherein the bacterial strain is of the species Blautia hydrogenotrophica, Blautia stercoris, Blautia wexlerae or Blautia producta.

7. The composition for use according to any preceding claim, wherein the bacterial strain is of the species Blautia hydrogenotrophica.

8. The composition for use according to any one of daims 1-7, wherein the bacterial strain has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to the I6s rRNA sequence of a bacterial strain of Blautia hydrogenotrophica.

9. The composition for use according to daim 8, wherein (a) the bacterial strain has a 16s rRNA sequence that is at least 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO:5 or which has the 16s rRNA sequence of SEQ ID NO:5, or (b) the bacterial strain has a 16s rRNA sequence that is at least 97%, 98%, 99%, 99.5% or 99.9% identical to any one of SEQ ID NOs:6-8 or which has the 16s rRNA sequence of any one of SEQ ID NOs:6-8.

10. A composition comprising a bacterial strain of the species Blautia hydrogenotrophica for use in:

(a) treating or preventing sensory hypersensitivity in a subject diagnosed with fibromyalgia; or (b) treating or preventing allodynia and/or hyperalgesia which are both associated with sensory hypersensitivity in a subject diagnosed with fibromyalgia; or (c) treating or preventing fibromyalgia.

11. The composition for use according to claim 10, wherein the composition is for use in a patient who has not been diagnosed with viscéral hypersensitivity.

12. The composition for use according to any preceding claim, wherein:

(a) the composition is for oral administration; and/or

5 (b) the composition comprises one or more pharmaceutically acceptable excipients or carriers;

and/or (c) the bacterial strain is lyophilised or viable.

13. The composition for use according to any preceding claim, wherein the composition comprises (a ) the Blautia hydrogenotrophica bacterial strain as part of a microbial consortium, or (b) only bacterîa 10 of the species Blautia hydrogenotrophica.

14, The composition for use according to any preceding claim, wherein the composition does not comprise bacterîa oi'the genus Clostridium.

15. The composition for use according to any preceding claim, wherein the bacterial strain has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID 15 NO:5.

16. The composition for use according to any preceding claim, wherein the composition is formulated as a probiotic and/or wherein the composition comprises a prebiotic compound.

17. The composition for use according to claim 16, wherein the prebiotic compound is a nondigestible carbohydrate or a sugar alcohol.

20 18. The composition for use according to claim 17, wherein the non-digestible carbohydrate is selected from the group consisting of: fructo-oligosaccharides (or FOS), short-chain fructooligosaccharides, inulin, isomalt-oligosaccharides, pectins, xylo-oligosaceharides (or XOS), chitosanoligosaccharides (or COS), beta-glucans, arable gum modified and résistant starches, polydextrose, Dtagatose, acacia fibers, carob, oats, and citrus fïbers.

25 19. The compositions for use according to any preceding claim, wherein the composition comprises granules or gelatin capsules.