U.S. patent application number 15/524808 was filed with the patent office on 2019-12-19 for faecalibacterium prausnitzii strains for treating and preventing gastrointestinal pain.
This patent application is currently assigned to INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE (INRA). The applicant listed for this patent is ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (APHP), ECOLE D'INGENIEURS DE PURPAN, INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE (INRA), INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM), UNIVERSITE PIERRE ET MARIE CURIE (PARIS 6). Invention is credited to Luis BERMUDEZ HUMARAN, Frederic CARVALHO, Philippe LANGELLA, Rebeca MARTIN ROSIQUE, Sylvie MIQUEL, Harry SOKOL, Vassilia THEODOROU, Muriel THOMAS.
Application Number | 20190381115 15/524808 |
Document ID | / |
Family ID | 52000767 |
Filed Date | 2019-12-19 |
United States Patent
Application |
20190381115 |
Kind Code |
A1 |
LANGELLA; Philippe ; et
al. |
December 19, 2019 |
FAECALIBACTERIUM PRAUSNITZII STRAINS FOR TREATING AND PREVENTING
GASTROINTESTINAL PAIN
Abstract
The present invention relates to a bacterial strain of the
Faecalibacterium prausnitzii species selected from a bacterial
strain belonging to one of the phylogroups I, II and III, for use
in the treatment and/or prevention of visceral abdominal pain in an
individual. The present invention also concerns compositions
comprising said bacterial strains as well as specific strains as
such.
Inventors: |
LANGELLA; Philippe;
(Velizy-Villacoublay, FR) ; MIQUEL; Sylvie;
(Beaumont, FR) ; MARTIN ROSIQUE; Rebeca; (Jouy en
Josas, FR) ; BERMUDEZ HUMARAN; Luis; (Jouy en Josas,
FR) ; THOMAS; Muriel; (Igny, FR) ; SOKOL;
Harry; (Paris, FR) ; CARVALHO; Frederic;
(Clermont-Ferrand, FR) ; THEODOROU; Vassilia;
(Portet Sure Garonne, FR) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE (INRA)
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
(INSERM)
UNIVERSITE PIERRE ET MARIE CURIE (PARIS 6)
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (APHP)
ECOLE D'INGENIEURS DE PURPAN |
Paris
Paris
Paris Cedex 05
Paris
Toulouse |
|
FR
FR
FR
FR
FR |
|
|
Assignee: |
INSTITUT NATIONAL DE LA RECHERCHE
AGRONOMIQUE (INRA)
Paris
FR
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
(INSERM)
Paris
FR
UNIVERSITE PIERRE ET MARIE CURIE (PARIS 6)
Paris Cedex 05
FR
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (APHP)
Paris
FR
ECOLE D'INGENIEURS DE PURPAN
Toulouse
FR
|
Family ID: |
52000767 |
Appl. No.: |
15/524808 |
Filed: |
November 13, 2015 |
PCT Filed: |
November 13, 2015 |
PCT NO: |
PCT/EP2015/076572 |
371 Date: |
May 5, 2017 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A23L 33/135 20160801;
C12R 1/01 20130101; A61P 29/00 20180101; A61K 35/741 20130101 |
International
Class: |
A61K 35/741 20060101
A61K035/741; A23L 33/135 20060101 A23L033/135; A61P 29/00 20060101
A61P029/00 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 13, 2014 |
EP |
14306803.9 |
Claims
1. A method of treating and/or preventing visceral abdominal pain
in an individual, comprising administering to the individual a
therapeutically effective amount of at least one Faecalibacterium
prausnitzii bacterial strain belonging to phylogroup I, II and/or
III.
2. The method according to claim 1, wherein the at least one
Faecalibacterium prausnitzii bacterial strain belongs to phylogroup
I and/or phylogroup III.
3. The method according to claim 1, wherein the at least one
Faecalibacterium prausnitzii bacterial strain belongs to phylogroup
I and is selected from the group consisting of bacterial strains
deposited to the CNCM under accession numbers I-4542, I-4544 and
I-4540.
4. The method according to claim 1, wherein the at least one
Faecalibacterium prausnitzii bacterial strain belongs to phylogroup
III and is selected from the group consisting of bacterial strains
deposited to the CNCM under accession numbers I-4574, I-4543,
I-4575, I-4573, I-4644 and I-4546.
5. The method according to claim 1, wherein the at least one
Faecalibacterium prausnitzii bacterial strain is selected from the
group consisting of bacterial strains deposited to the CNCM under
the accession numbers I-4542, I-4544, I-4540, I-4574, I-4543,
I-4575, I-4573, I-4644 and I-4546.
6. The method according to claim 1, wherein the visceral abdominal
pain is a gastrointestinal pain.
7. The method according to claim 1, wherein the visceral abdominal
pain is caused by a gastrointestinal disorder.
8. The method according to claim 7, wherein the gastrointestinal
disorder is a gastrointestinal hypersensitivity.
9. The method according to claim 1, wherein the bacterial strain is
comprised in a composition comprising a physiologically acceptable
medium.
10. A composition comprising, in a physiologically acceptable
medium, at least one bacterial strain of Faecalibacterium
prausnitzii selected from the group consisting of bacterial strains
deposited to the CNCM under the accession numbers I-4542, I-4544,
I-4540, I-4574, I-4543, I-4575, I-4573, I-4644 and I-4546.
11. The composition according to claim 10, wherein the at least one
bacterial strain of Faecalibacterium prausnitzii is the bacterial
strain deposited to the CNCM under the accession number I-4573.
12. The composition according to claim 10, wherein the composition
is for oral administration and is selected from the group
consisting of a food product, a drink, a pharmaceutical, a
nutraceutical, a food additive, a food supplement and a dairy
product.
13. An isolated bacterial strain selected from the group consisting
of bacterial strains deposited to the CNCM under the accession
numbers I-4542, I-4544, I-4540, I-4574, I-4543, I-4575, I-4573,
I-4644 and I-4546.
14. The isolated bacterial strain according to claim 13, being the
bacterial strain deposited to the CNCM under the accession number
I-4573.
15. The method of claim 5, wherein the at least one
Faecalibacterium prausnitzii bacterial strain is a bacterial strain
deposited to the CNCM under accession number I-4573.
16. The method of claim 6, wherein the gastrointestinal pain is a
colonic pain.
17. The method according to claim 7, wherein the gastrointestinal
disorder is a non-inflammatory gastrointestinal disorder.
18. The method according to claim 8, wherein the gastrointestinal
hypersensitivity is a colonic hypersensitivity selected from
Irritable Bowel Syndrome and alternating-type Irritable Bowel
Syndrome.
19. The method according to claim 9, wherein the physiologically
acceptable medium is a food supplement.
20. The composition of claim 12, wherein the composition is a food
supplement.
Description
FIELD OF THE INVENTION
[0001] The present invention concerns Faecalibacterium prausnitzii
strains for use in the treatment and prevention of visceral
abdominal pain in an individual, in particular of gastrointestinal
pain of non-inflammatory origin.
[0002] The present invention also concerns a composition, in
particular an oral composition, comprising specific
Faecalibacterium prausnitzii strains as well as new
Faecalibacterium prausnitzii strains per se.
PRIOR ART
[0003] Visceral abdominal pain, and in particular gastrointestinal
pain, is a very common disorder that affects millions of people
every year all over the world and is a leading cause of patient
visits to clinics. Abdominal pain is present on questioning of 75
percent of otherwise healthy adolescent students (Hyams et al. J.
Pediatr. 1996; 129:220) and in about half of all adults (Heading;
Scand J Gastroenterol Suppl. 1999; 231:3).
[0004] Such visceral pain can originate from various origins such
as peptic disease, pancreatitis in alcoholics, inflammatory bowel
disease, appendicitis, ruptured viscus, acute volvulus or even
gastritis, biliary colic, gastroenteritis, splenic rupture, hepatic
laceration or small bowel rupture.
[0005] However, gastrointestinal disorders, in particular
non-inflammatory gastrointestinal disorders, and more particularly
Irritable Bowel Syndrome (IBS), are the most frequent reasons for
visceral abdominal pain in an individual.
[0006] IBS is one of the 25 most wide-spread recognized pathologies
of the gastrointestinal tract. In the USA and in the first five
European countries (France, Germany, the United Kingdom, Spain and
Italy), in 2009, IBS affected more than 24 million persons. IBS
accounts for 40 to 60% of referrals to gastroenterology outpatient
clinics (Jones et al., Gut 2000; 47(Suppl 2): ii1-ii19).
[0007] Three subgroups of IBS patients have been defined based on
the predominant bowel habit: constipation-predominant (c-IBS),
diarrhea-predominant (d-IBS) or alternating between 25 the two
(a-IBS). The definition and diagnostic criteria for IBS have been
formalized in the "Rome Criteria" (Drossman et al. 1999, Gut
45:Suppl II: 1-81).
[0008] The pathophysiology of IBS is believed to involve
alterations in the brain-gut axis. However, the mechanisms by which
these changes lead to IBS remain poorly understood.
[0009] IBS is in particular characterized by a colonic
hypersensitivity. This pain sensitivity is usually studied using
variation of balloon distention in the rectum, a procedure in which
a balloon is inserted into the rectum and slowly inflated. This
common complaint is a crucial feature because of its significant
impact on a patient's quality of life and lack of efficient
therapies.
[0010] However, the current treatments against IBS and visceral
abdominal pain are disappointing.
[0011] There is thus a need for new substances, in particular
probiotics, or compositions for the treatment and/or prevention of
visceral abdominal pain, in particular gastrointestinal pain, in an
individual.
[0012] There is also a need for new substances, in particular
probiotics, or compositions for preventing and/or treating visceral
abdominal pain in an individual suffering from a non-inflammatory
gastrointestinal disorder, in particular from an Irritable Bowel
Syndrome (IBS).
[0013] More particularly, there is a need in the prior art for new
substances, in particular probiotics, or compositions that are able
to diminish the sensitivity of nociceptors in the gastrointestinal
tract of an individual, in particular in individuals suffering from
a colonic hypersensitivity.
SUMMARY OF THE INVENTION
[0014] The present invention aims to provide novel substances, in
particular probiotics, and compositions for treating and/or
preventing visceral abdominal pain in an individual, more
particularly gastrointestinal pain of non-inflammatory origin.
[0015] According to the inventors' experimental results, specific
Faecalibacterium prausnitzii (F. prausnitzii) strains, belonging to
three particular phylogroups previously described (Lopez-Siles et
al., 2012), possess the unexpected ability to diminish visceral
abdominal pain in an individual. As illustrated in the Examples and
discussed further, the inventors have demonstrated that F.
prausnitzii strains outside of these phylogroups, such as the
strain CNCM I-4541, do not possess such advantageous
properties.
[0016] The properties of the F. prausnitzii strains of the
invention have been demonstrated in the examples by the inventor's
in two different models: a Neonatal Maternal Separation (NMS)
colonic hypersensitivity (CHS) mouse model and a Partial Restraint
Stress (PRS) rat model.
[0017] Strains according to the invention are more particularly
able to diminish the sensitivity of nociceptors in the
gastrointestinal tract of an individual and consequently to prevent
and/or reduce colonic hypersensitivity of said individual.
[0018] According to a first object, the present invention relates
to a bacterial strain of the Faecalibacterium prausnitzii species
selected from a bacterial strain belonging to one of the
phylogroups I, II and III according to the invention, for use in
the treatment and/or prevention of visceral abdominal pain in an
individual.
[0019] These strains identified by the inventors are thus
probiotics that can be used for the above-indicated purposes.
[0020] An individual according to the invention is a mammal, in
particular a human.
[0021] Visceral abdominal pain is pain associated with organs of
the abdomen of the individual.
[0022] The visceral abdominal pain is in particular a
gastrointestinal pain, in particular a colonic pain.
[0023] A bacterial strain of the Faecalibacterium prausnitzii
species according to the invention is different from the strain
A2-165.
[0024] According to a preferred embodiment, bacterial strains
according to the invention for use as indicated here above are
selected from the group consisting of bacterial strains deposited
to the CNCM under the accession numbers I-4542, I-4544, I-4540,
I-4574, I-4543, I-4575, I-4573, I-4644 and I-4546, and in
particular the bacterial strain deposited to the CNCM under the
accession number I-4573.
[0025] According to an embodiment, the visceral pain according to
the invention is caused by a gastrointestinal disorder, in
particular a non-inflammatory gastrointestinal disorder.
[0026] A gastrointestinal disorder of the invention, in particular
according to this embodiment, can be a gastrointestinal
hypersensitivity, in particular a colonic hypersensitivity, and is
preferably an Irritable Bowel Syndrome, in particular an
alternating-type Irritable Bowel Syndrome.
[0027] In particular, such gastrointestinal disorder according to
the invention can be selected from the group consisting of IBS and
constipation.
[0028] According to another embodiment, a bacterial strain for use
according to the invention is comprised in a composition comprising
a physiologically acceptable medium, preferably in an oral
composition, and most preferably in a food supplement.
[0029] Thus, according to another object, the present invention
relates to a composition comprising, in a physiologically
acceptable medium, at least one bacterial strain of
Faecalibacterium prausnitzii selected from the group consisting of
bacterial strains deposited to the CNCM under the accession numbers
I-4542, I-4544, I-4540, I-4574, I-4543, I-4575, I-4573, I-4644 and
I-4546.
[0030] In a preferred embodiment, said bacterial strain of the
Faecalibacterium prausnitzii species is the bacterial strain
deposited to the CNCM under the accession numbers I-4573.
[0031] The term "physiologically acceptable medium" is understood
to mean a medium that is compatible with the organism of the
individual to whom said composition is intended to be administered.
It can for example be any non-toxic solvent such as water. In
particular, said medium is compatible with an oral
administration.
[0032] A composition of the invention is preferably for the oral
route and in particular in the form of a food supplement.
[0033] A composition of the invention for the oral route can be
selected from the group consisting of a food product, a drink, a
pharmaceutical, a nutraceutical, a food additive, a food supplement
and a dairy product. It can in particular be a food supplement.
[0034] The inventors have also indentified new Faecalibacterium
prausnitzii strains having the specific abilities discussed
previously.
[0035] Consequently, a further object of the invention consists in
an isolated bacterial strain selected from the group consisting of
bacterial strains deposited to the CNCM under the accession numbers
I-4542, I-4544, I-4540, I-4574, I-4543, I-4575, I-4573, I-4644 and
I-4546.
[0036] According to a preferred embodiment, said bacterial strain
is the bacterial strain deposited to the CNCM under the accession
number I-4573.
[0037] As demonstrated in the examples, a Faecalibacterium
prausnitzii strain of the invention has no negative impact in an
individual not suffering from visceral abdominal pain according to
the invention and is thus perfectly safe for use.
FIGURES' LEGENDS
[0038] FIG. 1A illustrates the variation of the Vicero Motrice
Response (VMR--mV/s) of a colon depending on the Distension volume
(4) of a balloon inserted into the rectum and slowly inflated, in
non-handled (NH) (normal lines) or Maternal separated (MS) (bold
lines) mice pre-treated with PBS (dotted lines) or with CNCM I-4573
(full lines) bacteria according to the invention.
[0039] FIG. 1B illustrates the variation of the Vicero Motrice
Response (VMR--mV/s) of a colon depending on the Distension volume
(tt) of a balloon inserted into the rectum and slowly inflated, in
non-handled (NH) (normal lines) or Maternal separated (MS) (bold
lines) mice pre-treated with PBS (dotted lines) or with CNCM I-4541
(full lines) bacteria outside of the invention.
[0040] FIG. 2 illustrates 35 Faecalibacterium prausnitzii strains
and their distribution in or outside of the three phylogroups of
the invention.
[0041] For illustrative purposes, Faecalibacterium prausnitzii
strains CNCM I-4541 (SEQ ID No: 16) and 513E3 (SEQ ID No: 17) are
outside the three phylogroups of the invention. The method for
obtaining said distribution is discussed further below.
[0042] FIG. 3A illustrates the effect of F. prausnitzii CNCM I-4573
strain on the number of abdominal cramps/5 minutes in Partial
Restraint Stress (PRS) (PRS-4573--continuous slashed line; n=12
rats) or basal rats models (Basal-4573--continuous lines with
circles; n=12 rats) compared to PRS or basal rats treated with PBS
(respectively PRS-PBS--dotted slashed lines and Basal-PBS--dotted
lines with circles; n=18 rats per group), depending on the
Distension volume (mL) generated with an arterial embolectomy
catheter introduced into the rectum of the rats.
[0043] FIG. 3B illustrates the effect of F. prausnitzii CNCM I-4541
strain outside of the invention on the number of abdominal cramps/5
minutes in Partial Restraint Stress (PRS) (PRS-4573--continuous
slashed line; n=12 rats) or basal rats models
(Basal-4573--continuous lines with circles; n=12 rats) compared to
PRS or basal rats treated with PBS (respectively PRS-PBS--dotted
slashed lines and Basal-PBS--dotted lines with circles; n=18 rats
per group), depending on the Distension volume (mL) generated with
an arterial embolectomy catheter introduced into the rectum of the
rats.
DETAILED DESCRIPTION OF THE INVENTION
[0044] The present inventors have performed a huge amount of work
with the view of identifying the ability of specific
Faecalibacterium prausnitzii strains to treat and/or prevent
visceral abdominal pain, and in particular gastrointestinal pain,
in an individual.
[0045] The inventors have indeed unexpectedly determined that
Faecalibacterium prausnitzii strains belonging to three phylogroups
defined further exhibit the ability to diminish the sensitivity of
nociceptors in the gastrointestinal tract of an individual.
[0046] The bacterial strains according to the invention can prevent
and/or reduce visceral abdominal pain, in particular
gastrointestinal pain, in an individual, in particular in an
individual suffering from a gastrointestinal non-inflammatory
disorder, and in particular from a colonic hypersensitivity, such
as in IBS.
[0047] It is demonstrated herein that bacterial strains of the
invention are in particular able to reduce the Vicero Motrice
Response (VMR) of a colon when a balloon inserted into the rectum
is slowly inflated in an IBS mouse model pre-treated with a
bacterial strain of the invention. Said VMR is brought back to a
normal intensity, since the VMR level observed after administration
of a strain according to the invention is similar to the VMR
observed in mice not suffering from colonic hypersensitivity.
[0048] Faecalibacterium prausnitzii Strains of the Invention
[0049] F. prausnitzii is a major member of the Firmicutes phylum
and is part of the most abundant commensal bacteria in the healthy
human large intestine microbiota. F. prausnitzii is an extremely
oxygen sensitive (EOS) bacterium and is thus difficult to
cultivate, even in anaerobic conditions (Duncan et al. 2002, Int.
J. Syst. Evol. Microbiol. 52(Pt 6): 2141-6 and Lopez-Siles et al.
Appl. Environ Microbiol. 2012 January;78(2):420-8). F. prausnitzii
is in particular known as being one of the most abundant
butyrate-producing bacterium in the human gastrointestinal tract,
the short chain fatty acid butyrate being very important in gut
physiology, systemic functions and beneficial effects for human
health (Macfarlane and Macfarlane (2011), J. Clin. Gastroenterol.
45 Suppl: S120-7).
[0050] F. prausnitzii is also known for having anti-inflammatory
and protective effects in murine models of acute and chronic
colitis, i.e. in inflammatory disorders (Martin et al., Inflamm
Bowel Dis. 2014 March; 20(3):417-30 and Sokol et al., Proc Natl
Acad Sci USA. 2008 Oct. 28;105(43):16731-6).
[0051] Recently, diminished prevalence and abundance of F.
prausnitzii have been reported in non-inflammatory intestinal
disorders. A negative correlation has indeed been observed between
the abundance of F. prausnitzii bacteria and IBS symptoms, in
particular in alternating-type IBS.
[0052] Emerging evidences suggest that perturbation of the
gastrointestinal microbiota, and in particular dysbiosis, plays a
role in the pathophysiology of IBS (Ringel and Maharshak, Am. J.
Physiol. Gastrointest. Liver Physiol. 2013 Oct. 15; 305(8):
G529-41).
[0053] The ability of the F. prausnitzii strains of the invention
to prevent visceral abdominal pain, and in particular
gastrointestinal pain, in an individual is specific to the strains
identified by the inventors, and constituting the three phylogroups
of the invention.
[0054] Such specific antinociceptive activity is illustrated in the
examples, wherein a comparative test has been performed with a F.
prausnitzii strain not part of the three phylogroups of the
invention, i.e. the strain CNCM I-4541. As demonstrated in these
examples, this strain does not possess the antinociceptive activity
of the strains of the invention.
[0055] Method for Obtaining Phylogroups of the Invention
[0056] Isolated Faecalibacterium prausnitzii strains have been
classified by the inventors in three phylogroups illustrated in
FIG. 2 according to 16S rRNA sequences.
[0057] Full-length 16S rRNA gene sequences of each strain were
obtained or determined and compared one to the other.
[0058] Full-length 16S rRNA sequences of 17 F. prausnitzii strains
are indicated as sequences SEQ ID No: 1 to 17.
[0059] DNA was extracted from isolated colonies of the different F.
prausnitzii strains by alkaline lysis in 50 .mu.L of NaOH 0.5 M
during 30 min and 50 .mu.l of Tris 1M pH7 and 100 .mu.L H.sub.2O
were added.
[0060] 16S rRNA sequences were amplified and PCR products purified
with the Wizard SV Gel. PCR Clean-Up system (Promega) was used to
obtain bidirectional partial 16S rRNA gene sequences by using
primers. All DNA sequences were confirmed by sequencing (Eurofins
MWG Operon, Ebersberg, Germany).
[0061] Multiple sequence alignment was performed with hierarchical
clustering for 16S rRNA gene sequence full-length construction
(http://multalin.toulouse.inrafr/multalin) (COrpet F., Nucleic
Acids Res. 1988; 16:10881-10890).
[0062] Phylogenetic analysis of the 16S rRNA gene was then
performed using MEGA6 software package
(http://www.megasoftware.net/). The evolutionary history was
inferred using the Neighbor-Joining method (Saitou N. and Nei M.,
Mol Biol Evol. 1987; 4:406-425).
[0063] The optimal tree with the sum of branch length=0.24930207 is
shown in FIG. 2. The percentage of replicate trees in which the
associated taxa clustered together in the bootstrap test (500
replicates) are shown next to the branches (Zharkikh A. and Li WH,
Mol Phylogenet Evol. 1995; 4:44-63).
[0064] The tree is drawn to scale, with branch lengths in the same
units as those of the evolutionary distances used to infer the
phylogenetic tree. The evolutionary distances were computed using
the Maximum Composite Likelihood method (Tamura et al., Proc Natl
Acad Sci USA. 2004; 101:11030-11035) and are in the units of the
number of base substitutions per site.
[0065] The analysis involved 35 nucleotide sequences. Codon
positions included were lst+2nd+3rd+Non-coding. All positions
containing gaps and missing data were eliminated.
[0066] There were a total of 1091 positions in the final
dataset.
[0067] Eubacterium desmolans was used to root the tree (SEQ ID No:
18). In sequence SEQ ID No: 18, `n` is used to represent any
ambiguous nucleotides.
[0068] In order to verify if a given F. prausnitzii strain can be
classified in one of the phylogroups I to III according to the
invention, its 16S rRNA sequence needs to be compared through the
MEGA6 software package discussed here-above directly to the one of
the present invention.
[0069] According to an embodiment, a bacterial strain of the
invention is selected from phylogroup I.
[0070] Bacterial strains belonging to phylogroup I can be
represented by the strains consisting of: [0071] bacterial strains
deposited to the CNCM under the accession numbers I-4542, I-4544
and I-4540; and [0072] bacterial strains of reference HTF-75H,
S13A7, S3G1, L2-15, L2-39, L2-61 and L2-6.
[0073] Preferably, a bacterial strain belonging to phylogroup I is
selected from the group consisting of bacterial strains deposited
to the CNCM under the accession numbers I-4542, I-4544 and
I-4540.
[0074] According to an embodiment, a bacterial strain of the
invention is selected from phylogroup II.
[0075] Bacterial strains belonging to phylogroup I1 can for example
be selected from the group consisting of bacterial strains of
reference HTF-60C, HTF-I, HTF-E, HTF-C, HTF-A, HTF-B and HTF-F.
[0076] According to an embodiment, a bacterial strain of the
invention is selected from phylogroup III.
[0077] Bacterial strains belonging to phylogroup III can be
represented by the strains consisting of: [0078] bacterial strains
deposited to the CNCM under the accession numbers I-4574, I-4543,
I-4575, I-4573, I-4644 and I-4546; and [0079] bacterial strains of
reference S3C12, S9G3, S9D8, S3L/3, S4L/4, M21/2 and S10H3, with
the proviso that the bacterial strain is different from the
bacterial strain A2-165.
[0080] Preferably, a bacterial strain belonging to phylogroup III
is selected from the group consisting of bacterial strains
deposited to the CNCM under the accession numbers I-4574, I-4543,
I-4575, I-4573, I-4644 and I-4546.
[0081] Bacterial strains of reference ATCC 27768, A2-165, L2-15,
L2-39, L2-6, L2-61, M21/2, S3L/3, S4L/4, HTF-A, HTF-B, HTF-C,
HTF-E, HTF-F, HTF-I, HTF-60C and HTF-75H can be obtained as
indicated in Lopez-Siles et al., Appl. Environ. Microbiol. 2012,
78(2):420.
[0082] In a preferred embodiment, a bacterial strain of the
invention is selected from phylogroups I and/or III. More
particularly, a bacterial strain of the invention is selected from
phylogroups I and/or III with the proviso that the bacterial strain
is different from the bacterial strain A2-165.
[0083] According to an embodiment, a bacterial strain of the
invention is selected from the group consisting of bacterial
strains deposited to the CNCM under the accession numbers I-4542,
I-4544, I-4540, I-4574, I-4543, I-4575, I-4573, I-4644 and
I-4546.
[0084] A bacterial strain of the invention is preferably the
bacterial strain deposited to the CNCM under the accession number
I-4573.
[0085] The inventors have also indentified new Faecalibacterium
prausnitzii strains having the specific abilities discussed
previously.
[0086] Consequently, the present invention further concerns an
isolated bacterial strain selected from the group consisting of
bacterial strains deposited to the CNCM under the accession numbers
I-4542, I-4544, I-4540, I-4574, I-4543, I-4575, I-4573, I-4644 and
I-4546.
[0087] Said bacterial strain is in particular the bacterial strain
deposited to the CNCM under the accession number I-4573.
[0088] A suitable daily dose of a bacterial strain according to the
invention is from 10.sup.3 to 10.sup.12 colony forming units (cfu),
more preferably from 10.sup.7 to 10.sup.11 cfu as a medicament, for
example as a daily dose equivalent to 10.sup.10 cfu.
[0089] A Faecalibacterium prausnitzii strain of the invention is
for use in the treatment and/or prevention of visceral abdominal
pain in an individual.
[0090] The strains of the invention are probiotics whose activity
lies in the gut. A probiotic bacterium according to the invention
denotes a bacterium which ingested live in adequate quantities can
exert beneficial effects on the human health.
[0091] These strains consequently need to be administered alive to
the gut.
[0092] The bacteria strains of the invention can be administered to
the gut of an individual to be treated by different ways, i.e. by
the oral, rectal or parenteral route. A bacterium according to the
invention is preferably administered by the oral or rectal route,
more preferably by the oral route.
[0093] According to a preferred embodiment, a bacterial strain of
the invention is comprised in a composition comprising a
physiologically acceptable medium. Such composition is preferably
for the oral route, and in particular in the form of a food
supplement.
[0094] Compositions
[0095] The present invention further concerns a composition
comprising, in a physiologically acceptable medium, at least one
bacterial strain of Faecalibacterium prausnitzii of the
invention.
[0096] More particularly, according to an embodiment, the present
invention relates to a composition comprising, in a physiologically
acceptable medium, at least one bacterial strain of
Faecalibacterium prausnitzii selected from the group consisting of
bacterial strains deposited to the CNCM under the accession numbers
I-4542, I-4544, I-4540, I-4574, I-4543, I-4575, I-4573, I-4644 and
I-4546.
[0097] Preferably, a composition according to the invention
comprises at least one bacterial strain deposited to the CNCM under
the accession number I-4573.
[0098] A composition according to the invention is intended for the
gastrointestinal tract, in particular the gut.
[0099] Consequently, a composition according to the invention is
selected from an oral, rectal or parenteral composition. A
composition of the invention is preferably an oral or rectal
composition, more preferably an oral composition.
[0100] According to an embodiment, a composition of the invention
is an oral composition, i.e. is intended for oral administration to
a subject.
[0101] Such composition can be in the form of a suspension, tablet,
pill, capsule, granulate or powder.
[0102] The composition according to the invention for the oral
route can be selected from the group consisting of a food product,
a drink, a pharmaceutical, a nutraceutical, a food additive, a food
supplement or a dairy product, and is in particular a food
supplement.
[0103] According to a preferred embodiment, a composition according
to the invention is a food supplement.
[0104] Food supplement for oral administration may be present in
capsules, gelatin capsules, soft capsules, tablets, sugar-coated
tablets, pills, pastes, pastilles, gums, drinkable solutions or
emulsions, a syrup or a gel.
[0105] Advantageously, a composition according to the invention,
intended for oral administration, can be provided with a coating
resistant to gastric juice, so as to ensure that the bacterial
strain of the invention comprised in said composition can pass
through the stomach undamaged. The release of the bacterial strain
can thus takes place for the first time in the upper intestinal
tract.
[0106] A food supplement according to the invention can also
include a sweetener, a stabilizer, an antioxidant, an additive, a
flavouring agent and/or a colorant.
[0107] The formulation thereof is carried out by means of the usual
methods for producing sugar-coated tablets, gel capsules, gels,
hydrogels for controlled release, emulsions, tablets or
capsules.
[0108] A composition according to the invention can also be in the
form of a nutritional composition.
[0109] A nutritional composition according to the invention is in
the form of a yogurt, a cereal bar, a breakfast cereal, a dessert,
a frozen food, a soup, a pet food, a liquid suspension, a powder, a
tablet, a gum or a candy.
[0110] In a further embodiment of the invention, a composition
containing a bacterial strain of the invention is administered
intrarectally.
[0111] A rectal administration preferably takes place in the form
of a suppository, enema or foam.
[0112] A composition according to the invention contains an amount
of bacterial strains of the invention equivalent to between
10.sup.3 and 10.sup.12 cfu/g (dry weight basis), more preferably
between 10.sup.6 and 10.sup.9 cfu/g.
[0113] A composition according to the invention can further
comprise at least one of: antioxidants, fish oils, DHA, EPA,
vitamins, minerals, phytonutrients, protein, fat, probiotics, and
combinations thereof.
[0114] The present invention further concerns the use of at least
one bacterial strain of the Faecalibacterium prausnitzii species
selected from a bacterial strain belonging to at least one of the
phylogroups I, II and III, for the treatment and/or prevention of
visceral abdominal pain in an individual.
[0115] The present invention also concerns the use of a
composition, preferably an oral composition, comprising, in a
physiologically acceptable medium, at least one bacterial strain of
the Faecalibacterium prausnitzii species selected from a bacterial
strain belonging to at least one of the phylogroups I, II and III,
for the treatment and/or prevention of visceral abdominal pain in
an individual.
[0116] The invention will be described below in greater details
using the following examples which are given for illustrative
purposes only.
[0117] All references to percentages are percentages by weight
unless otherwise stated.
EXAMPLES
[0118] F. prausnitzii strains according to the invention have been
tested for their ability to have a direct impact on visceral pain,
and more particularly on colonic hypersensitivity.
[0119] Bacterial Strains Isolation and Growth Conditions
[0120] The F. prausnitzii strains isolates used in the present
example all are of human fecal origin from healthy patients. Said
isolates were obtained from the highest countable dilution of human
fecal samples in roll tubes of anaerobic M2GSC medium as discussed
in Lopez-Sites et al. (Appl. Environ Microbiol. 2012;
78:420-428).
[0121] Tested F. prausnitzii strains isolates were grown in LYBHI
medium (Brain-Heart infusion medium supplemented with 0.5% yeast
extract) (Dyfco, Detroit, USA) supplemented with 1 mg/mL cellobiose
(Sigma-Aldrich Chemie Gmbh, Buchs, Switzerland), 1 mg/mL maltose
(Sigma-Aldrich) and 0.5 mg/mL cysteine (Sigma-Aldrich) at
37.degree. C. in anaerobic chamber.
[0122] A. In a first series of tests, a Neonatal Maternal
Separation (NMS) colonic hypersensitivity (CHS) mouse model is
used.
[0123] a. NMS CHS Mouse Model
[0124] Pregnant C57Bl/6J mice have been purchased from Janvier
laboratories (Le Genest Saint Isle, France).
[0125] After birth, wild-type C57Bl/6J were isolated from their
mother from D2 to D14, three hours a day, from 9 a.m. to 12 a.m. At
nine-week old age, male mice were orally treated each day for nine
days with 200 .mu.L of 10.times.10.sup.10 CFU/mL of: [0126] the
strain CNCM I-4573 according to the invention; [0127] the strain
CNCM I-4541 outside the invention; or [0128] PBS as control.
[0129] All the experiments were performed on the last day of
treatment at D10.
[0130] The same bacteria treatment was administered to non-NMS CHS
mice as a control.
[0131] NMS treatment induced an increased Vicero Motrice Response
(VMR) in the absence of any significant alteration in gut wall
macroscopic integrity or colonic mucosa inflammation (Coutinho et
al. (2002), Am. J. Physiol. Gastrointest. Liver Physiol. 282(2):
G307-16).
[0132] As described in Christianson et al. 2007 (Nat Protoc 2(10):
2624-31), colonic sensitivity was assessed by quantifying
visceromotor response with abdominal electromyography (EMG)
recordings in response to colorectal distension.
[0133] The inventors also validated this model as being
non-inflammatory by checking the cytokines pattern by measurement
of 13 types of cytokines in serum samples of stressed (MS: Maternal
separated) and non-stressed (NH: Non-handled) mice.
[0134] It was observed that there are no differences in cytokine
pattern induced by the chronic stress.
[0135] Moreover, NMS does not induce changes in colonic macroscopic
damage, loss of architectural epithelium, goblet cell depletion,
oedema/ulceration or inflammatory cell infiltrates.
[0136] Furthermore, NMS does not induce changes in body weight,
colon weight and length and in spleen weight when stressed (MS)
mice are compared to the control group (PBS).
[0137] b. Statistical Analysis
[0138] Statistical analysis was completed using GraphPad software
(GraphPad Software, La Jolla, Calif., USA). All data were expressed
as mean+/-SEM.
[0139] MS mice displaying VMR values lower than mean minus two SEM
for all distension volumes were considered as non-sensitized and
excluded from the analysis.
[0140] For VMR analysis in model validation, a two-way (Volume
& Treatment) ANOVA followed by Bonferroni post-hoc test for
multiple comparisons was used.
[0141] P<0.05 was considered statistically significant.
[0142] c. Results
[0143] The results obtained are presented in FIGS. 1A and 1B.
[0144] As it can be seen in FIG. 1A, control Maternal separated
(MS) mice, to whom only PBS was administered, present a high VMR,
two times higher than the VMR of the non-handled (NH) mice, treated
with CNCM I-4573 bacteria or only with PBS.
[0145] More importantly, it can be seen that MS mice to whom CNCM
I-4573 bacteria of the invention were administered possess a VMR
statistically similar to the one of NH mice, all along the growth
of the Volume Distension.
[0146] On the contrary, in FIG. 1B, there is no statistical
difference between the results obtained with MS mice only treated
with PBS or treated with CNCM I-4541 bacteria.
[0147] Treatment based on the administration of F. prausnitzii
strain CNCM I-4573 according to the invention led to a specific and
significant decrease of the VMR in the tested mice as well as a
prevention of the increase of the VMR.
[0148] On the contrary, the treatments based on the control tests
(NH mice) and on the administration of F. prausnitzii strain CNCM
I-4541 present no effect on the VMR of all the tested mice.
[0149] The present results clearly demonstrate that F. prausnitzii
strains according to the invention have a specific and unexpected
beneficial effect on visceral abdominal pain.
[0150] B. In a second series of tests, a Partial Restreint Stress
(PRS) rat model is used.
[0151] a. Partial Restraint Stress (PRS) Rat Model
[0152] Animal preparation was performed as previously described in
Ait-Belgnaoui et al.; Gut 55, 1090-1094 (2006).
[0153] Briefly, under general anesthesia induced by i.p.
administration of 0.6 mg/kg acepromazine (Calmivet, Vetoquinol,
Lure, France) and 120 mg/kg ketamine (Imalgene 1000, Merial, Lyon,
France), female Wistar rats (Rosztoczy, A. et al.;
Neurogastroenterol. Motil. Off. J. Eur. Gastrointest. Motil. Soc.
15, 679-686 (2003)) were equipped with three groups of three NiCr
wire electrodes (60 cm in length, 80 nm in diameter) implanted into
the abdominal external oblique muscle, 2 cm above the inguinal
ligament.
[0154] Electrodes were exteriorized at the neck level by a glass
tube attached to the skin.
[0155] During the ten days previous to the stress, 1 ml of
.+-.1.times.10.sup.9 CFU or PBS were daily intragastrically
administrated.
[0156] The study groups are as follows: [0157] the strain CNCM
I-4573 according to the invention; [0158] the strain CNCM I-4541
outside the invention; or [0159] PBS as control.
[0160] All stress sessions were performed at the same time of the
day (between 10 am and 12 pm) to minimize any influence of
circadian rhythms. Stresses were performed using the wrap partial
restrain stress model which is a mild non-ulcerogenic stressor
(Williams, C. L et al.; Am. J. Physiol. 253, G582-586 (1987)).
[0161] Animals were lightly anesthetized (as previously described
in Lee B. et al.; J. Neurogastroenterol. Motil. 17, 252-266 (2011),
with ethyl-ether and their fore shoulders, upper forelimbs and
thoracic trunk were draped in a confining harness of paper tape to
restrict, but not to prevent, body movements.
[0162] Then rats were placed in their home cage for 2 h.
[0163] b. Rectal or Colorectal Distension and Colonic
Hypersensitivity Measurement
[0164] Rats colonic sensitivity induced by PRS was assessed by
quantifying electrical response through an electroencephalograph
Reega Mini-hui (ALVAR, France) and expressed as number of abdominal
cramps for a five min period (as previously described in Eutamene,
H. et al.; J. Physiol. 506 (Pt 1), 245-252 (1998)).
[0165] Briefly, rats were accustomed to be in polypropylene tunnels
(diameter 7 cm, length 20 cm) several days before colorectal
distension (CRD) in order to minimize recording artifacts.
[0166] CRD was performed with an arterial embolectomy catheter
(Fogarty; Edwards Laboratoire, Inc., Santa Ana, Calif., USA)
introduced into the rectum (1 cm from the anus) and fixed at the
base of the tail.
[0167] Distension of the colon was performed by connecting the
catheter to a syringe and consecutive injections of different
volumes (0.4, 0.8, 1.2 ml) with an interval of 5 minutes.
[0168] Each animal was recorded two days before the stress (basal
measure) and just after the PRS (stress measure).
[0169] c. Statistical Analysis.
[0170] Statistical analysis was completed using GraphPad software
(GraphPad Sofware, La Jolla, Calif., USA).
[0171] Results are presented with means.+-.SEM.
[0172] Differences in the number of abdominal cramps during 5
minutes to gradual CRD volumes were analyzed using a 2-way ANOVA
(Treatment, Volume) followed by Bonferroni post-hoc test for
multiple comparisons.
[0173] A p value of less than 0.05 was considered significant.
[0174] d. Results
[0175] To determine if F. prausnitzii CNCMI-4541 (outside of the
invention) and CNCMI-4573 (according to the invention) strains are
able to prevent acute stress generated symptoms on visceral
sensitivity, both were tested on a model of Partial Restraint
Stress (PRS).
[0176] PRS increased the number of abdominal cramps in response to
CRD in a volume-dependent manner (FIGS. 3A and 3B).
[0177] In stressed rats treated with PBS, distensions at any
volumes significantly increased the number of abdominal
contractions compared to non-stressed animals (p<0.01) (FIGS. 3A
and 3B).
[0178] F. prausnitzii CNCMI-4573 strain treatment prevented this
stress-induced visceral hypersensitivity until 0.8 ml distension
volume (p<0.001) (FIG. 3A).
[0179] In basal conditions, no difference was observed in the VMR
to CRD between the different treatments (FIG. 3A).
[0180] In contrast, F. prausnitzii CNCMI-4541 strain did not show a
protective effect (FIG. 3B).
[0181] In conclusion, it appears that a F. prausnitzii strain
according to the invention prevents visceral hypersensitivity in a
model of Partial Restraint Stress (PRS).
TABLE-US-00001 SEQ ID No: 1: 16S rRNA sequence of F. prausnitzii
CNCM I-4540 AGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACA
CATGCAAGTCGAACGAGTGAGAGAGAGCTTGCTTTCTCGAGCGAGTGGCGAAC
GGGTGAGTAACGCGTGAGGAACCTGCCTCAAAGAGGGGGACAACAGTTGGAA
ACGACTGCTAATACCGCATAAGCCCACGGCTCGGCATCGAGCAGAGGGAAAA
GGAGTGATCCGCTTTGAGATGGCCTCGCGTCCGATTAGCTAGTTGGTGAGGTA
ATGGCCCACCAAGGCGACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCAC
ATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATA
TTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGGAGGAAGAAGGT
CTTCGGATTGTAAACTCCTGTTGTTGGGGAAGATAATGACGGTACCCAACAAG
GAAGTGACGGCTAACTACGTGCCAGCAGCCGCGGTAAAACGTAGGTCACAAG
CGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGCAGGCGGGGAGACAAGTTG
GAAGTGAAATCTATGGGCTCAACCCATAAACTGCTTTCAAAACTGTTTTTCTTG
AGTAGTGCAGAGGTAGGCGGAATTCCCGGTGTAGCGGTGGAATGCGTAGATAT
CGGGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCACCAACTGACGCTGA
GGCTCGAAAGTGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACACCG
TAAACGATGATTACTAGGTGTTGGAGGATTGACCCCTTCAGTGCCGCAGTTAA
CACAATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGG
AATTGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGACGCAAC
GCGAAGAACCTTACCAAGTCTTGACATCCCTTGACAGACATAGAAATATGTAT
TCTCTTCGGAGCAAGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGT
GAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATGGTCAGTTACTAC
GCAAGAGGACTCTGGCCAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGAT
GACGTCAAATCATCATGCCCTTTATGACTTGGGCTACACACGTACTACAATGGC
GTTAAACAAAGAGAAGCAAGACCGCGAGGTGGAGCAAAACTCAGAAACAACG
TCCCAGTTCGGACTGCAGGCTGCAACTCGCCTGCACGAAGTCGGAATTGCTAG
TAATCGTGGATCAGCATGCCACGGTGAATACGTTCCCGGGCCTTGTACACACC
GCCCGTCACACCATGAGAGCCGGGGGGACCCGAAGTCGGTAGTCTAACCGCA
AGGAGGACGCCGCCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGTAACAAG GTAGCCGT SEQ
ID No: 2: 16S rRNA sequence of F. prausnitzii CNCM I-4542
AGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACA
CATGCAAGTCGAACGAGCGAGAGAGAGCTTGCTTTCTCGAGCGAGTGGCGAAC
GGGTGAGTAACGCGTGAGGAACCTGCCTCAAAGAGGGGGACAACAGTTGGAA
ACGACTGCTAATACCGCATAAGCCCACGGGTCGGCATCGACCAGAGGGAAAA
GGAGCAATCCGCTTTGAGATGGCCTCGCGTCCGATTAGCTAGTTGGTGAGGTA
ATGGCCCACCAAGGCAACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCAC
ATTGGGACTGAGACGCGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATA
TTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGGAGGAAGAAGGT
CTTCGGATTGTAAACTCCTGTTGTTGGGGAAGATAATGACGGTACCCAACAAG
GAAGTGACGGCTAACTACGTGCCAGCAGCCGCGGTAAAACGTAGGTCACAAG
CGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGCAGGCGGGAAGACAAGTTG
GAAGTGAAATCTATGGGCTCAACCCATAAACTGCTTTCAAAACTGTTTTTCTTG
AGTAGTGCAGAGGTAGGCGGAATTCCCGGTGTAGCGGTGGAATGCGTAGATAT
CGGGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCACCAACTGACGCTGA
GGCTCGAAAGTGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACACCG
TAAACGATGGTTACTAGGTGTTGGAGGATTGACCCCTTCAGTGCCGCAGTTAA
CACAATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGG
AATTGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGACGCAAC
GCGAAGAACCTTACCAAGTCTTGACATCCCTTGACAGACATAGAAATATGTAA
TCTCTTCGGAGCAAGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGT
GAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATGGTCAGTTACTAC
GCAAGAGGACTCTGGCCAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGAT
GACGTCAAATCATCATGCCCTTTATGACTTGGGCTACACACGTACTACAATGGC
GTTAAACAAAGAGAAGCAAGACCGCGAGGTGGAGCAAAACTCAGAAACAACG
TCCCAGTTCGGACTGCAGGCTGCAACTCGCCTGCACGAAGTCGGAATTGCTAG
TAATCGTGGATCAGCATGCCACGGTGAATACGTTCCCGGGCCTTGTACACACC
GCCCGTCACACCATGAGAGCCGGGGGGACCCGAAGTCGGTAGTCTAACCGCA
AGGAGGACGCCGCCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGTAACAAG GTAGCCGT SEQ
ID No: 3: 16S rRNA sequence of F. prausnitzii S3C12
GCGAGAGAGAGCTTGCTTTCTCGAGCGAGTGGCGAACGGGTGAGTA
ACGCGTGAGGAACCTGCCTCAAAGAGGGGGACAACAGTTGGAAACGACTGCT
AATACCGCATAAGCCCACGGCCCGGCATCGGGCAGAGGGAAAAGGAGCAATC
CGCTTTGAGATGGCCTCGCGTCCGATTAGCTAGTTGGTGAGGTAACGGCCCAC
CAAGGCGACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACT
GAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAAT
GGGGGAAACCCTGATGCAGCGACGCCGCGTGGAGGAAGAAGGTCTTCGGATT
GTAAACTCCTGTTGTTGAGGAAGATAATGACGGTACTCAACAAGGAAGTGACG
GCTAACTACGTGCCAGCAGCCGCGGTAAAACGTAGGTCACAAGCGTTGTCCGG
AATTACTGGGTGTAAAGGGAGCGCAGGCGGGAAGACAAGTTGGAAGTGAAAT
CCATGGGCTCAACCCATGAACTGCTTTCAAAACTGTTTTTCTTGAGTAGTGCAG
AGGTAGGCGGAATTCCCGGTGTAGCGGTGGAATGCGTAGATATCGGGAGGAA
CACCAGTGGCGAAGGCGGCCTACTGGGCACCAACTGACGCTGAGGCTCGAAA
GTGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACACCGTAAACGATG
ATTACTAGGTGTTGGAGGATTGACCCCTTCAGTGCCGCAGTTAACACAATAAG
TAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGG
GGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGACGCAACGCGAAGAAC
CTTACCAAGTCTTGACATCCTGCGACGGTTCTGGAAACAGAACTTTCCTTCGGG
ACGCAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGG
GTTAAGTCCCGCAACGAGCGCAACCCTTATGGTCAGTTACTACGCAAGAGGAC
TCTGGCCAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAAT
CATCATGCCCTTTATGACTTGGGCTACACACGTACTACAATGGCGTTAAACAA
AGAGAAGCAAGACCGCGAGGTGGAGCAAAACTCAGAAACAACGTCCCAGTTC
GGACTGCAGGCTGCAACTCGCCTGCACGAAGTCGGAATTGCTAGTAATCGTGG
ATCAGCATGCCACGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAC
ACCATGAGAGCCGGGGGGACCCGAAGTCGGTAGTCTAACCGCAAGGAGGACG
CCGCCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGTAACAAGGTAG SEQ ID No: 4: 16S
rRNA sequence of F. prausnitzii S3G1
AGCGAGAGAGAGCTTGCTTTCTCGAGCGAGTGGCGAACGGGTGAGT
AACGCGTGAGGAACCTGCCTCAAAGAGGGGGACAACAGTTGGAAACGACTGC
TAATACCGCATAAGCCCACGGTGCCGCATGGCACAGAGGGAAAAGGAGCAAT
CCGCTTTGAGATGGCCTCGCGTCCGATTAGCTAGTTGGTGAGGTAACGGCCCA
CCAAGGCGACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGAC
TGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAA
TGGGGGAAACCCTGATGCAGCGACGCCGCGTGGAGGAAGAAGGTCTTCGGAT
TGTAAACTCCTGTTGTTGGGGAAGATAATGACGGTACCCAACAAGGAAGTGAC
GGCTAACTACGTGCCAGCAGCCGCGGTAAAACGTAGGTCACAAGCGTTGTCCG
GAATTACTGGGTGTAAAGGGAGCGCAGGCGGGAAGACAAGTTGGAAGTGAAA
TCTATGGGCTCAACCCATAAACTGCTTTCAAAACTGTTTTTCTTGAGTAGTGCA
GAGGTAGGCGGAATTCCCGGTGTAGCGGTGGAATGCGTAGATATCGGGAGGA
ACACCAGTGGCGAAGGCGGCCTACTGGGCACCAACTGACGCTGAGGCTCGAA
AGTGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACACCGTAAACGAT
GATTACTAGGTGTTGGAGGATTGACCCCTTCAGTGCCGCAGTTAACACAATAA
GTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACG
GGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGACGCAACGCGAAGA
ACCTTACCAAGTCTTGACATCCCTTGACAGGCATAGAAATATGTTTTCTCTTCG
GAGCAAGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTT
GGGTTAAGTCCCGCAACGAGCGCAACCCTTATGGTCAGTTACTACGCAAGAGG
ACTCTGGCCAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAA
ATCATCATGCCCTTTATGACTTGGGCTACACACGTACTACAATGGCGTTAAACA
AAGAGAAGCAAGACCGCGAGGTGGAGCAAAACTCAGAAACAACGTCCCAGTT
CGGACTGCAGGCTGCAACTCGCCTGCACGAAGTCGGAATTGCTAGTAATCGTG
GATCAGCATGCCACGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCA
CACCATGAGAGCCGGGGGGACCCGAAGTCGGTAGTCTAACCGCAAGGAGGAC
GCCGCCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGTAACAAG SEQ ID No: 5: 16S rRNA
sequence of F. prausnitzii CNCM I-4574
CGAGTGGCGAACGGGTGAGTAACGCGTGAGGAACCTGCCTCAAAG
AGGGGGACAACAGTTGGAAACGACTGCTAATACCGCATAAGCCCACAGGTCG
GCATCGACCAGAGGGAAAAGGAGCAATCCGCTTTGAGATGGCCTCGCGTCCGA
TTAGCTAGTTGGTGAGGTAATGGCCCACCAAGGCAACGATCGGTAGCCGGACT
GAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGG
AGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGACGC
CGCGTGGAGGAAGAAGGTCTTCGGATTGTAAACTCCTGTTGTTGAGGAAGATA
ATGACGGTACTCAACAAGGAAGTGACGGCTAACTACGTGCCAGCAGCCGCGGT
AAAACGTAGGTCACAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGCA
GGCGGGAAGACAAGTTGGAAGTGAAATCTATGGGCTCAACCCATAAACTGCTT
TCAAAACTGTTTTTCTTGAGTAGTGCAGAGGTAGGCGGAATTCCCGGTGTAGC
GGTGGAATGCGTAGATATCGGGAGGAACACCAGTGGCGAAGGCGGCCTACTG
GGCACCAACTGACGCTGAGGCTCGAAAGTGTGGGTAGCAAACAGGATTAGAT
ACCCTGGTAGTCCACACCGTAAACGATGATTACTAGGTGTTGGAGGATTGACC
CCTTCAGTGCCGCAGTTAACACAATAAGTAATCCACCTGGGGAGTACGACCGC
AAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGTGGAGTATG
TGGTTTAATTCGACGCAACGCGAAGAACCTTACCAAGTCTTGACATCCTGTGA
CGATGCTGGAAACATGTTTTTCCTTCGGAACGCAGAGACAGGTGGTGCATGGT
TGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAAC
CCTTACTGTCAGTTACTACGCAAGAGGACTCTGGCAGGACTGCCGTTGACAAA
ACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCTTTATGACTTGGGCT
ACACACGTACTACAATGGCGTTAAACAAAGAGAAGCAAGACCGCGAGGTGGA
GCAAAACTCAGAAACAACGTCCCAGTTCGGACTGCAGGCTGCAACTCGCCTGC
ACGAAGTCGGAATTGCTAGTAATCGTGGATCAGCATGCCACGGTGAATACGTT
CCCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGCCGGGGGGACCCGAA
GTCGGTAGTCTAACCGCAAGGAGGACGCCGCCGAAGGTAAAACTGGTGATTG
GGGTGAAGTCGTAACAAGGTAGCC SEQ ID No: 6: 16S rRNA sequence of F.
prausnitzii CNCM I-4543
CGAGCGAGAGAGAGCTTGCTTTCTCAATCGAGTGGCGAACGGGTGA
GTAACGCGTGAGGAACCTGCCTCAAAGAGGGGGACAACAGTTGGAAACGACT
GCTAATACCGCATAAGCCCACAGGTCGGCATCGACCAGAGGGAAAAGGAGCA
ATCCGCTTTGAGATGGCCTCGCGTCCGATTAGCTAGTTGGTGAGGTAATGGCCC
ACCAAGGCAACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGA
CTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACA
ATGGGGGAAACCCTGATGCAGCGACGCCGCGTGGAGGAAGAAGGTCTTCGGA
TTGTAAACTCCTGTTGTTGAGGAAGATAATGACGGTACTCAACAAGGAAGTGA
CGGCTAACTACGTGCCAGCAGCCGCGGTAAAACGTAGGTCACAAGCGTTGTCC
GGAATTACTGGGTGTAAAGGGAGCGCAGGCGGGAAGACAAGTTGGAAGTGAA
ATCTATGGGCTCAACCCATAAACTGCTTTCAAAACTGTTTTTCTTGAGTAGTGC
AGAGGTAGGCGGAATTCCCGGTGTAGCGGTGGAATGCGTAGATATCGGGAGG
AACACCAGTGGCGAAGGCGGCCTACTGGGCACCAACTGACGCTGAGGCTCGA
AAGTGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACACCGTAAACGA
TGATTACTAGGTGTTGGAGGATTGACCCCTTCAGTGCCGCAGTTAACACAATA
AGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGAC
GGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGACGCAACGCGAAG
AACCTTACCAAGTCTTGACATCCTGTGACGAACCTGGAAATATGTTTTTCCTTC
GGAACGCAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGT
TGGGTTAAGTCCCGCAACGAGCGCAACCCTTACTGTCAGTTACTACGCAAGAG
GACTCTGGCAGGACTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCA
AATCATCATGCCCTTTATGACTTGGGCTACACACGTACTACAATGGCGTTAAAC
AAAGAGAAGCAAGACCGCGAGGTGGAGCAAAACTCAGAAACAACGTCCCAGT
TCGGACTGCAGGCTGCAACTCGCCTGCACGAAGTCGGAATTGCTAGTAATCGT
GGATCAGCATGCCACGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTC
ACACCATGAGAGCCGGGGGGACCCGAAGTCGGTAGTCTAACCGCAAGGAGGA
CGCCGCCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGTACAG SEQ ID No: 7: 16S rRNA
sequence of F. prausnitzii S9D8
AGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACA
CATGCAAGTCGAACGAGCGAGAGAGAGCTTGCTTTCTCGAGCGAGTGGCGAAC
GGGTGAGTAACGCGTGGGGAACCTGCCTCAAAGAGGGGGACAACAGTTGGAA
ACGACTGCTAATACCGCATAAGCCCACGACCTGGCATCGGGTTGAGGGAAAAG
GAGCAATCCGCTTTGAGATGGCCTCGCGTCCGATTAGCTAGTTGGTGAGGTAA
TGGCCCACCAAGGCAACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACA
TTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATT
GCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGGAGGAAGAAGGTCT
TCGGATTGTAAACTCCTGTTGTTGAGGAAGATAATGACGGTACTCAACAAGGA
AGTGACGGCTAACTACGTGCCAGCAGCCGCGGTAAAACGTAGGTCACAAGCGT
TGTCCGGAATTACTGGGTGTAAAGGGAGCGCAGGCGGGAAGACAAGTTGGAA
GTGAAATCCATGGGCTCAACCCATGAACTGCTTTCAAAACTGTTTTTCTTGAGT
AGTGCAGAGGTAGGCGGAATTCCCGGTGTAGCGGTGGAATGCGTAGATATCGG
GAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCACCAACTGACGCTGAGGC
TCGAAAGTGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACACCGTAA
ACGATGATTACTAGGTGTTGGAGGATTGACCCCTTCAGTGCCGCAGTTAACAC
AATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATT
GACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGACGCAACGCGA
AGAACCTTACCAAGTCTTGACATCCTGCGACGGTGCTGGAAACAGTGCTTTCCT
TCGGGACGCAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGAT
GTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATGGTCAGTTACTACGCAAG
AGGACTCTGGCCAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGT
CAAATCATCATGCCCTTTATGACTTGGGCTACACACGTACTACAATGGCGTTAA
ACAAAGAGAAGCAAGACCGCGAGGTGGAGCAAAACTCAGAAACAACGTCCCA
GTTCGGACTGCAGGCTGCAACTCGCCTGCACGAAGTCGGAATTGCTAGTAATC
GTGGATCAGCATGCCACGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCG
TCACACCATGAGAGCCGGGGGGACCCGAAGTCGGTAGTCTAACCGCAAGGAG
GACGCCGCCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGTAACAAGGTAGC CGT SEQ ID No:
8: 16S rRNA sequence of F. prausnitzii S9G3
GCATGCTCGAGCGGCCGCCAGTGTGATGGATATCTGCAGAATTCGC
CCTTAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACAT
GCAAGTCGAACGAGCGAGAGAGAGCTTGCTTTCTCGAGCGAGTGGCGAACGG
GTGAGTAACGCGTGAGGAACCTGCCTCAAAGAGGGGGACAACAGTTGGAAAC
GACTGCTAATACCGCATAAGCCCACGACCCGGCATCGGGTAGAGGGAAAAGG
AGCAATCCGCTTTGAGATGGCCTCGCGTCCGATTAGCTAGTTGGTGAGGTAAC
GGCCCACCAAGGCGACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACAT
TGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATT
GCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGGAGGAAGAAGGTCT
TCGGATTGTAAACTCCTGTTGTTGAGGAAGATAATGACGGTACTCAACAAGGA
AGTGACGGCTAACTACGTGCCAGCAGCCGCGGTAAAACGTAGGTCACAAGCGT
TGTCCGGAATTACTGGGTGTAAAGGGAGCGCAGGCGGGAAGACAAGTTGGAA
GTGAAATCCATGGGCTCAACCCATGAACTGCTTTCAAAACTGTTTTTCTTGAGT
AGTGCAGAGGTAGGCGGAATTCCCGGTGTAGCGGTGGAATGCGTAGATATCGG
GAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCACCAACTGACGCTGAGGC
TCGAAAGTGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACACCGTAA
ACGATGATTACTAGGTGTTGGAGGATTGACCCCTTCAGTGCCGCAGTTAACAC
AATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATT
GACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGACGCAACGCGA
AGAACCTTACCAAGTCTTGACATCCTGCGACGGTTCTGGAAACAGAACTTTCCT
TCGGGACGCAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGAT
GTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATGGTCAGTTACTACGCAAG
AGGACTCTGGCCAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGT
CAAATCATCATGCCCTTTATGACTTGGGCTACACACGTACTACAATGGCGTTAA
ACAAAGAGAAGCAAGACCGCGAGGTGGAGCAAAACTCAGAAACAACGTCCCA
GTTCGGACTGCAGGCTGCAACTCGCCTGCACGAAGTCGGAATTGCTAGTAATC
GTGGATCAGCATGCCACGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCG
TCACACCATGAGAGCCGGGGGGACCCGAAGTCGGTAGTCTAACCGCAAGGAG
GACGCCGCCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGTAACAAGGTAGC CGTAAGGGCGAA
SEQ ID No: 9: 16S rRNA sequence of F. prausnitzii CNCM I-4644
GCATCGGGCAGAGGGAAAAGGAGCAATCCGCTTTGAGATGGCCTC
GCGTCCGATTAGCTAGTTGGTGAGGTAATGGCCCACCAAGGCGACGATCGGTA
GCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACT
CCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGC
AGCGACGCCGCGTGGAGGAAGAAGGTCTTCGGATTGTAAACTCCTGTTGTTGA
GGAAGATAATGACGGTACTCAACAAGGAAGTGACGGCTAACTACGTGCCAGC
AGCCGCGGTAAAACGTAGGTCACAAGCGTTGTCCGGAATTACTGGGTGTAAAG
GGAGCGCAGGCGGGAAGACAAGTTGGAAGTGAAATCCATGGGCTCAACCCAT
GAACTGCTTTCAAAACTGTTTTTCTTGAGTAGTGCAGAGGTAGGCGGAATTCCC
GGTGTAGCGGTGGAATGCGTAGATATCGGGAGGAACACCAGTGGCGAAGGCG
GCCTACTGGGCACCAACTGACGCTGAGGCTCGAAAGTGTGGGTAGCAAACAG
GATTAGATACCCTGGTAGTCCACACTGTAAACGATGATTACTAGGTGTTGGAG
GATTGACCCCTTCAGTGCCGCAGTTAACACAATAAGTAATCCACCTGGGGAGT
ACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGT
GGAGTATGTGGTTTAATTCGACGCAACGCGAAGAACCTTACCAAGTCTTGACA
TCCTGCGACGCACATAGAAATATGTGTTTCCTTCGGGACGCAGAGACAGGTGG
TGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGA
GCGCAACCCTTATGGTCAGTTACTACGCAAGAGGACTCTGGCCAGACTGCCGT
TGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCTTTATGAC
TTGGGCTACACACGTACTACAATGGCGTTAAACAAAGAGAAGCAAGACCGCG
AGGTGGAGCAAAACTCAGAAACAACGTCCCAGTTCGGACTGCAGGCTGCAACT
CGCCTGCACGAAGTCGGAATTGCTAGTAATCGCAGATCAGCATGCTGCGGTGA
ATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGCCGGGGGG
ACCCGAAGTCGGTAGTCTAACCGCAAGGAGGACGCCGCCGAAGGTAAAACTG
GTGATTGGGGTGAAGTCGTAACAAGGTAG SEQ ID No: 10: 16S rRNA sequence of
F. prausnitzii CNCM I-4544
CGAGCGAGAGAGAGCTTGCTTTCTCGAGCGAGTGGCGAACGGGTGA
GTAACGCGTGAGGAACCTGCCTCAAAGAGGGGGACAACAGTTGGAAACGACT
GCTAATACCGCATAAGCCCACGGGTCGGCATCGACCAGAGGGAAAAGGAGCA
ATCCGCTTTGAGATGGCCTCGCGTCCGATTAGCTAGTTGGTGAGGTAACGGCC
CACCAAGGCAACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGG
ACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCAC
AATGGGGGAAACCCTGATGCAGCGACGCCGCGTGGAGGAAGAAGGTCTTCGG
ATTGTAAACTCCTGTTGTTGGGGAAGATAATGACGGTACCCAACAAGGAAGTG
ACGGCTAACTACGTGCCAGCAGCCGCGGTAAAACGTAGGTCACAAGCGTTGTC
CGGAATTACTGGGTGTAAAGGGAGCGCAGGCGGGAAGACAAGTTGGAAGTGA
AATCTATGGGCTCAACCCATAAACTGCTTTCAAAACTGTTTTTCTTGAGTAGTG
CAGAGGTAGGCGGAATTCCCGGTGTAGCGGTGGAATGCGTAGATATCGGGAG
GAACACCAGTGGCGAAGGCGGCCTACTGGGCACCAACTGACGCTGAGGCTCG
AAAGTGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACACCGTAAACG
ATGATTACTAGGTGTTGGAGGATTGACCCCTTCAGTGCCGCAGTTAACACAAT
AAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGA
CGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGACGCAACGCGAAG
AACCTTACCAAGTCTTGACATCCCTTGACAGACATAGAAATATGTAATCTCTTC
GGAGCAAGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGT
TGGGTTAAGTCCCGCAACGAGCGCAACCCTTATGGTCAGTTACTACGCAAGAG
GACTCTGGCCAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCA
AATCATCATGCCCTTTATGACTTGGGCTACACACGTACTACAATGGCGTTAAAC
AAAGAGAAGCAAGACCGCGAGGTGGAGCAAAACTCAGAAACAACGTCCCAGT
TCGGACTGCAGGCTGCAACTCGCCTGCACGAAGTCGGAATTGCTAGTAATCGT
GGATCAGCATGCCACGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTC
ACACCATGAGAGCCGGGGGGACCCGAAGTCGGTAGTCTAACCGCAAGGAGGA
CGCCGCCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGTAACAAG SEQ ID No: 11: 16S
rRNA sequence of F. prausnitzii S10H3
GAGCGAGTGGCGAACGGGTGAGTAACGCGTGAGGAACCTGCCTCA
AAGAGGGGGACAACAGTTGGAAACGACTGCTAATACCGCATAAGCCCACGAC
CCGGCATCGGGTAGAGGGAAAAGGAGCAATCCGCTTTGAGATGGCCTCGCGTC
CGATTAGCTAGTTGGTGAGGTAATGGCCCACCAAGGCGACGATCGGTAGCCGG
ACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACG
GGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGAC
GCCGCGTGGAGGAAGAAGGTCTTCGGATTGTAAACTCCTGTTGTTGAGGAAGA
TAATGACGGTACTCAACAAGGAAGTGACGGCTAACTACGTGCCAGCAGCCGCG
GTAAAACGTAGGTCACAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGC
AGGCGGGAAGACAAGTTGGAAGTGAAATCCATGGGCTCAACCCATGAACTGC
TTTCAAAACTGTTTTTCTTGAGTAGTGCAGAGGTAGGCGGAATTCCCGGTGTAG
CGGTGGAATGCGTAGATATCGGGAGGAACACCAGTGGCGAAGGCGGCCTACT
GGGCACCAACTGACGCTGAGGCTCGAAAGTGTGGGTAGCAAACAGGATTAGA
TACCCTGGTAGTCCACACTGTAAACGATGATTACTAGGTGTTGGAGGATTGAC
CCCTTCAGTGCCGCAGTTAACACAATAAGTAATCCACCTGGGGAGTACGACCG
CAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGTGGAGTAT
GTGGTTTAATTCGACGCAACGCGAAGAACCTTACCAAGTCTTGACATCCTGCG
ACGCACATAGAAATATGTGTTTCCTTCGGGACGCAGAGACAGGTGGTGCATGG
TTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAA
CCCTTATGGTCAGTTACTACGCAAGAGGACTCTGGCCAGACTGCCGTTGACAA
AACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCTTTATGACTTGGGC
TACACACGTACTACAATGGCGTTAAACAAAGAGAAGCAAGACCGCGAGGTGG
AGCAAAACTCAGAAACAACGTCCCAGTTCGGACTGCAGGCTGCAACTCGCCTG
CACGAAGTCGGAATTGCTAGTAATCGCAGATCAGCATGCTGCGGTGAATACGT
TCCCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGCCGGGGGGACCCGA
AGTCGGTAGTCTAACCGCAAGGAGGACGCCGCCGAAGGTAAAACTGGTGATT
GGGGTGAAGTCGTAACAAG SEQ ID No: 12: 16S rRNA sequence of F.
prausnitzii S13A7 AGCTTGCTTTCTCGAGCGAGTGGCGAACGGGTGAGTAACGCGTGAG
GAACCTGCCTCAAAGAGGGGGACAACAGTTGGAAACGACTGCTAATACCGCA
TAAGCCCACGGGTCGGCATCGACCAGAGGGAAAAGGAGCAATCCGCTTTGAG
ATGGCCTCGCGTCCGATTAGCTAGTTGGTGAGGTAACGGCCCACCAAGGCGAC
GATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGG
CCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAAC
CCTGATGCAGCGACGCCGCGTGGAGGAAGAAGGTCTTCGGATTGTAAACTCCT
GTTGTTGGGGAAGATAATGACGGTACCCAACAAGGAAGTGACGGCTAACTAC
GTGCCAGCAGCCGCGGTAAAACGTAGGTCACAAGCGTTGTCCGGAATTACTGG
GTGTAAAGGGAGCGCAGGCGGGAAGACAAGTTGGAAGTGAAATCTATGGGCT
CAACCCATAAACTGCTTTCAAAACTGTTTTTCTTGAGTAGTGCAGAGGTAGGCG
GAATTCCCGGTGTAGCGGTGGAATGCGTAGATATCGGGAGGAACACCAGTGGC
GAAGGCGGCCTACTGGGCACCAACTGACGCTGAGGCTCGAAAGTGTGGGTAG
CAAACAGGATTAGATACCCTGGTAGTCCACACCGTAAACGATGATTACTAGGT
GTTGGAGGATTGACCCCTTCAGTGCCGCAGTTAACACAATAAGTAATCCACCT
GGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCAC
AAGCAGTGGAGTATGTGGTTTAATTCGACGCAACGCGAAGAACCTTACCAAGT
CTTGACATCCCTTGACAGACATAGAAATATGTATTCTCTTCGGAGCAAGGAGA
CAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCC
GCAACGAGCGCAACCCTTATGGTCAGTTACTACGCAAGAGGACTCTGGCCAGA
CTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCT
TTATGACTTGGGCTACACACGTACTACAATGGCGTTAAACAAAGAGAAGCAAG
ACCGCGAGGTGGAGCAAAACTCAGAAACAACGTCCCAGTTCGGACTGCAGGC
TGCAACTCGCCTGCACGAAGTCGGAATTGCTAGTAATCGTGGATCAGCATGCC
ACGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGC
CGGGGGGACCCGAAGTCGGTAGTCTAACCGCAAGGAGGACGCCGCCGAAGGT
AAAACTGGTGATTGGGGTGAAGTCGTAACAAG SEQ ID No: 13: 16S rRNA sequence
of F. prausnitzii CNCM I-4575
ATCGAGTGGCGAACGGGTGAGTAACGCGTGAGGAACCTGCCTCAA
AGAGGGGGACAACAGTTGGAAACGACTGCTAATACCGCATAAGCCCACGGCT
CGGCATCGAGCAGAGGGAAAAGGAGCAATCCGCTTTGAGATGGCCTCGCGTCC
GATTAGCTAGTTGGTGAGGTAATGGCCCACCAAGGCGACGATCGGTAGCCGGA
CTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGG
GAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGACG
CCGCGTGGAGGAAGAAGGTCTTCGGATTGTAAACTCCTGTTGTTGAGGAAGAT
AATGACGGTACTCAACAAGGAAGTGACGGCTAACTACGTGCCAGCAGCCGCG
GTAAAACGTAGGTCACAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGC
AGGCGGGCGATCAAGTTGGAAGTGAAATCCATGGGCTCAACCCATGAACTGCT
TTCAAAACTGATTGTCTTGAGTAGTGCAGAGGTAGGCGGAATTCCCGGTGTAG
CGGTGGAATGCGTAGATATCGGGAGGAACACCAGTGGCGAAGGCGGCCTACT
GGGCACCAACTGACGCTGAGGCTCGAAAGTGTGGGTAGCAAACAGGATTAGA
TACCCTGGTAGTCCACACCGTAAACGATGATTACTAGGTGTTGGAGGATTGAC
CCCTTCAGTGCCGCAGTTAACACAATAAGTAATCCACCTGGGGAGTACGACCG
CAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGTGGAGTAT
GTGGTTTAATTCGACGCAACGCGAAGAACCTTACCAAGTCTTGACATCCTGCG
ACGATGCTAGAAATAGTATTTTCCTTCGGGACGCAGAGACAGGTGGTGCATGG
TTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAA
CCCTTATGGTCAGTTACTACGCAAGAGGACTCTGGCCAGACTGCCGTTGACAA
AACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCTTTATGACTTGGGC
TACACACGTACTACAATGGCGTTAAACAAAGAGAAGCAAGACCGCGAGGTGG
AGCAAAACTCAGAAACAACGTCCCAGTTCGGACTGCAGGCTGCAACTCGCCTG
CACGAAGTCGGAATTGCTAGTAATCGCAGATCAGCATGCTGCGGTGAATACGT
TCCCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGCCGGGGGGACCCGA
AGTCGGTAGTCTAACCGCAAGGAGGACGCCGCCGAAGGTAAAACTGGTGATT
GGGGTGAAGTCGTAACAAGGTAGCCGTC SEQ ID No: 14: 16S rRNA sequence of F.
prausnitzii CNCM I-4573
GAGAGAGCTTGCTTTCTCAAGCGAGTGGCGAACGGGTGAGTAACGC
GTGAGGAACCTGCCTCAAAGAGGGGGACAACAGTTGGAAACGACTGCTAATA
CCGCATAAGCCCACGACCCGGCATCGGGTAGAGGGAAAAGGAGCAATCCGCT
TTGAGATGGCCTCGCGTCCGATTAGCTAGTTGGTGAGGTAACGGCCCACCAAG
GCGACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGA
CACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGG
GAAACCCTGATGCAGCGACGCCGCGTGGAGGAAGAAGGTCTTCGGATTGTAA
ACTCCTGTTGTTGAGGAAGATAATGACGGTACTCAACAAGGAAGTGACGGCTA
ACTACGTGCCAGCAGCCGCGGTAAAACGTAGGTCACAAGCGTTGTCCGGAATT
ACTGGGTGTAAAGGGAGCGCAGGCGGGAAGACAAGTTGGAAGTGAAATCCAT
GGGCTCAACCCATGAACTGCTTTCAAAACTGTTTTTCTTGAGTAGTGCAGAGGT
AGGCGGAATTCCCGGTGTAGCGGTGGAATGCGTAGATATCGGGAGGAACACC
AGTGGCGAAGGCGGCCTACTGGGCACCAACTGACGCTGAGGCTCGAAAGTGT
GGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACACTGTAAACGATGATTA
CTAGGTGTTGGAGGATTGACCCCTTCAGTGCCGCAGTTAACACAATAAGTAAT
CCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGC
CCGCACAAGCAGTGGAGTATGTGGTTTAATTCGACGCAACGCGAAGAACCTTA
CCAAGTCTTGACATCCTGCGACGGTGCTGGAAACAGTGCTTTCCTTCGGGACG
CAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTT
AAGTCCCGCAACGAGCGCAACCCTTATGGTCAGTTACTACGCAAGAGGACTCT
GGCCAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCAT
CATGCCCTTTATGACTTGGGCTACACACGTACTACAATGGCGTTAAACAAAGA
GAAGCAAGACCGCGAGGTGGAGCAAAACTCAGAAACAACGTCCCAGTTCGGA
CTGCAGGCTGCAACTCGCCTGCACGAAGTCGGAATTGCTAGTAATCGCAGATC
AGCATGCTGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACC
ATGAGAGCCGGGGGGACCCGAAGTCGGTAGTCTAACCGCAAGGAGGACGCCG
CCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGTAACAAG SEQ ID No: 15: 16S rRNA
sequence of F. prausnitzii CNCM I-4546
CAAGCGAGTGGCGAACGGGTGAGTAACGCGTGAGGAACCTGCCTC
AAAGAGGGGGACAACAGTTGGAAACGACTGCTAATACCGCATAAGCCCACGA
CCCGGCATCGGGTAGAGGGAAAAGGAGCAATCCGCTTTGAGATGGCCTCGCGT
CCGATTAGCTAGTTGGTGAGGTAACGGCCCACCAAGGCGACGATCGGTAGCCG
GACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTAC
GGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGA
CGCCGCGTGGAGGAAGAAGGTCTTCGGATTGTAAACTCCTGTTGTTGAGGAAG
ATAATGACGGTACTCAACAAGGAAGTGACGGCTAACTACGTGCCAGCAGCCGC
GGTAAAACGTAGGTCACAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCG
CAGGCGGGAAGACAAGTTGGAAGTGAAATCCATGGGCTCAACCCATGAACTG
CTTTCAAAACTGTTTTTCTTGAGTAGTGCAGAGGTAGGCGGAATTCCCGGTGTA
GCGGTGGAATGCGTAGATATCGGGAGGAACACCAGTGGCGAAGGCGGCCTAC
TGGGCACCAACTGACGCTGAGGCTCGAAAGTGTGGGTAGCAAACAGGATTAG
ATACCCTGGTAGTCCACACTGTAAACGATGATTACTAGGTGTTGGAGGATTGA
CCCCTTCAGTGCCGCAGTTAACACAATAAGTAATCCACCTGGGGAGTACGACC
GCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGTGGAGTA
TGTGGTTTAATTCGACGCAACGCGAAGAACCTTACCAAGTCTTGACATCCTGC
GACGCACATAGAAATATGTGTTTCCTTCGGGACGCAGAGACAGGTGGTGCATG
GTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCA
ACCCTTATGGTCAGTTACTACGCAAGAGGACTCTGGCCAGACTGCCGTTGACA
AAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCTTTATGACTTGGG
CTACACACGTACTACAATGGCGTTAAACAAAGAGAAGCAAGACCGCGAGGTG
GAGCAAAACTCAGAAACAACGTCCCAGTTCGGACTGCAGGCTGCAACTCGCCT
GCACGAAGTCGGAATTGCTAGTAATCGCAGATCAGCATGCTGCGGTGAATACG
TTCCCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGCCGGGGGGACCCG
AAGTCGGTAGTCTAACCGCAAGGAGGACGCCGCCGAAGGTAAAACTGGTGAT
TGGGGTGAAGTCGTAACAAGGGTAG SEQ ID No: 16: 16S rRNA sequence of F.
prausnitzii CNCM I-4541
AGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACA
CATGCAAGTCGAACGAGCGAGAGAGAGCTTGCTTTCTCGAGCGAGTGGCGAAC
GGGTGAGTAACGCGTGAGGAACCTGCCTCAAAGAGGGGGACAACAGTTGGAA
ACGACTGCTAATACCGCATAAGCCCACGACCCGGCATCGGGTTGAGGGAAAA
GGAGCAATCCGCTTTGAGATGGCCTCGCGTCCGATTAGCTAGTTGGTGAGGTA
ACGGCCCACCAAGGCGACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCAC
ATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATA
TTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGGAGGAAGAAGGT
CTTCGGATTGTAAACTCCTGTTGTTGGGGAAGATAATGACGGTACCCAACAAG
GAAGTGACGGCTAACTACGTGCCAGCAGCCGCGGTAAAACGTAGGTCACAAG
CGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGCAGGCGGGAAGACAAGTTG
GAAGTGAAATCCATGGGCTTAACCCATGAACTGCTTTCAAAACTGTTTTTCTTG
AGTAGTGCAGAGGTAGGCGGAATTCCCGGTGTAGCGGTGGAATGCGTAGATAT
CGGGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCACCAACTGACGCTGA
GGCTCGAAAGTGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACACCG
TAAACGATGATTACTAGGTGTTGGAGGATTGACCCCTTCAGTGCCGCAGTTAA
CACAATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGG
AATTGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGACGCAAC
GCGAAGAACCTTACCAAGTCTTGACATCCTGTGACAGACGTAGAAATACGTTC
TTCCTTCGGGACACAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGT
GAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATGGTCAGTTACTAC
GCAAGAGGACTCTGGCCAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGAT
GACGTCAAATCATCATGCCCTTTATGACTTGGGCTACACACGTACTACAATGGC
GTTAAACAAAGAGAAGCAAGACCGCGAGGTGGAGCAAAACTCAGAAACAACG
TCCCAGTTCGGACTGCAGGCTGCAACTCGCCTGCACGAAGTCGGAATTGCTAG
TAATCGTGGATCAGCATGCCACGGTGAATACGTTCCCGGGCCTTGTACACACC
GCCCGTCACACCATGAGAGCCGGGGGGACCCGAAGTCGGTAGTCTAACCGCA
AGGAGGACGCCGCCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGTAACAAG GTAGCCGT SEQ
ID No: 17: 16S rRNA sequence of F. prausnitzii S13E3
TTAGTGGCGAACGGGTGAGTAACGCGTGAGTAACCTGCCCTGGAGT
GGGGGACAACAGTTGGAAACGACTGCTAATACCGCATAAGCCCACGGCCCGG
CATCGGGCTGCGGGAAAAGGATTTATTCGCTTCAGGATGGACTCGCGTCCAAT
TAGCTAGTTGGTGAGGTAACGGCCCACCAAGGCGACGATTGGTAGCCGGACTG
AGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGA
GGCAGCAGTGGGGGATATTGCACAATGGGGGAAACCCTGATGCAGCGACGCC
GCGTGGAGGAAGAAGGTTTTCGGATTGTAAACTCCTGTCGTTAGGGACGAATC
ATGACGGTACCTAACAAGAAAGCACCGGCTAACTACGTGCCAGCAGCCGCGG
TAAAACGTAGGGTGCAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGCA
GGCGGACCGGCAAGTTGGAAGTGAAAACCATGGGCTCAACCCATGAATTGCTT
TCAAAACTGCTGGCCTTGAGTAGTGCAGAGGTAGGTGGAATTCCCGGTGTAGC
GGTGGAATGCGTAGATATCGGGAGGAACACCAGTGGCGAAGGCGACCTACTG
GGCACCAACTGACGCTGAGGCTCGAAAGCATGGGTAGCAAACAGGATTAGAT
ACCCTGGTAGTCCATGCCGTAAACGATGATTACTAGGTGTTGGAGGATTGACC
CCTTCAGTGCCGCAGTTAACACAATAAGTAATCCACCTGGGGAGTACGACCGC
AAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGTGGAGTATG
TGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCCGATGC
ATAGTGCAGAGATGCATGAAGTCCTTCGGGACATCGAGACAGGTGGTGCATGG
TTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAA
CCCTTATTGCCAGTTACTACGTAAGAGGACTCTGGCGAGACTGCCGTTGACAA
AACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCTTTATGACCTGGGC
TACACACGTACTACAATGGCGTTTAACAAAGAGAAGCAAGACCGCGAGGTGG
AGCAAAACTCAGAAACAACGTCTCAGTTCAGATTGCAGGCTGCAACTCGCCTG
CATGAAGTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGT
TCCCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGCCGGGGGGACCCGA AGTCGGTAGTCTA
SEQ ID No: 18: 16S rRNA sequence of Eubacterium desmolans ATCC
43058 TTTTTAGAGAGTTTGATCCTGGCTCAGGATNAACGCTGGCGGCGTGC
CTAACACATGCAAGTCGAACGGAGTTATTTTGGAAATCTCTTCGGAGATGGAA
TTCATAACTTAGTGGCGGACGGGTGAGTAACGCGTGAGCAATCTGCCTTTAGG
TGGGGGATAACAGTCGGAAACGGCTGCTAATACCGCATAATACGTTTTGGGGG
CATCCTTGAAACGTCAAAGATTTATTGCCTTTAGATGAGCTCGCGTCTGATTAG
CTGGTTGGCGGGGNAACGGCCCACCAAGGCGACGATCAGTAGCCGGACTGAG
AGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGG
CAGCAGTGGGGAATATTGCGCAATGGGGGAAACCCNGACGCAGCAACGCCGC
GTGATTGAAGAAGGCCTTCGGGTTGTAAAGATCTTTAATCAGGGACGAATTTT
GACGGTACCTGAAGAATAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAA
TACGTAGGGAGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGCGCAGNC
GGGNCGGCAAGTTGGGAGTGAAATCNGGGGGCTTAACCCCCGAACTGCTTTCA
AAACTGCTGGTCTTGAGTGATGGAGAGGCAGGCGGAATTCCGTGTGTAGCGGT
GAAATGCGTAGATATACGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGAC
ATTAACTGACGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACC
CTGGTAGTCCACGCCGTAAACGATGGATACTAGGTGTGGGAGGTATTGACCCC
TTCCGTGCCGCAGTTAACACAATAAGTATCCCACCTGGGGAGTACGGCCGCAA
GGTTGAAACTCAAAGGAATTGACGNNNGCCCGCACAAGCAGTGGAGTATGTG
GTTTAATTCGAANNAACGCGAAGAACCTTACCAGGNCTTGACATCCCGGTGAC
CGTCCTAGAGATAGGACTTNCCTTCGGGNCAACGGTGACAGNTGGTGCATGGT
TGTCGTCAGCTCGTGTCGTGAGATGTTGGNTTAAGTCCCGCAACGAGCGCAAC
CCTTACGGTTAGTTGATACGCAAGATCACTCTAGCCGGACTGCCGTTGACAAA
ACGGAGGAAGGTGGGGACGACGTNNAATCATCATGCCCCNTATGACCTGGGCT
ACACACGTACTACAATGGCAGTCATACAGAGGGAAGCAAAATCGCGAGGTGG
AGCAAATCCCTAAAAGCTGTCCCAGTTCAGATTGCAGGCTGCAACCCGCCTGC
ATGAAGTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTT
CCCGGGNNTTGTACACACCGCCCGTCACACCATGAGAGCCGTCAATACCCGAA
GTCCGTAGCCTAACCGCAAGGGGGGCGCGGCCGAAGGTAGGGGTGGTAAT
Sequence CWU 1
1
1811474DNAFaecalibacterium prausnitzii 1agagtttgat cctggctcag
gacgaacgct ggcggcgcgc ctaacacatg caagtcgaac 60gagtgagaga gagcttgctt
tctcgagcga gtggcgaacg ggtgagtaac gcgtgaggaa 120cctgcctcaa
agagggggac aacagttgga aacgactgct aataccgcat aagcccacgg
180ctcggcatcg agcagaggga aaaggagtga tccgctttga gatggcctcg
cgtccgatta 240gctagttggt gaggtaatgg cccaccaagg cgacgatcgg
tagccggact gagaggttga 300acggccacat tgggactgag acacggccca
gactcctacg ggaggcagca gtggggaata 360ttgcacaatg ggggaaaccc
tgatgcagcg acgccgcgtg gaggaagaag gtcttcggat 420tgtaaactcc
tgttgttggg gaagataatg acggtaccca acaaggaagt gacggctaac
480tacgtgccag cagccgcggt aaaacgtagg tcacaagcgt tgtccggaat
tactgggtgt 540aaagggagcg caggcgggga gacaagttgg aagtgaaatc
tatgggctca acccataaac 600tgctttcaaa actgtttttc ttgagtagtg
cagaggtagg cggaattccc ggtgtagcgg 660tggaatgcgt agatatcggg
aggaacacca gtggcgaagg cggcctactg ggcaccaact 720gacgctgagg
ctcgaaagtg tgggtagcaa acaggattag ataccctggt agtccacacc
780gtaaacgatg attactaggt gttggaggat tgaccccttc agtgccgcag
ttaacacaat 840aagtaatcca cctggggagt acgaccgcaa ggttgaaact
caaaggaatt gacgggggcc 900cgcacaagca gtggagtatg tggtttaatt
cgacgcaacg cgaagaacct taccaagtct 960tgacatccct tgacagacat
agaaatatgt attctcttcg gagcaaggag acaggtggtg 1020catggttgtc
gtcagctcgt gtcgtgagat gttgggttaa gtcccgcaac gagcgcaacc
1080cttatggtca gttactacgc aagaggactc tggccagact gccgttgaca
aaacggagga 1140aggtggggat gacgtcaaat catcatgccc tttatgactt
gggctacaca cgtactacaa 1200tggcgttaaa caaagagaag caagaccgcg
aggtggagca aaactcagaa acaacgtccc 1260agttcggact gcaggctgca
actcgcctgc acgaagtcgg aattgctagt aatcgtggat 1320cagcatgcca
cggtgaatac gttcccgggc cttgtacaca ccgcccgtca caccatgaga
1380gccgggggga cccgaagtcg gtagtctaac cgcaaggagg acgccgccga
aggtaaaact 1440ggtgattggg gtgaagtcgt aacaaggtag ccgt
147421474DNAFaecalibacterium prausnitzii 2agagtttgat cctggctcag
gacgaacgct ggcggcgcgc ctaacacatg caagtcgaac 60gagcgagaga gagcttgctt
tctcgagcga gtggcgaacg ggtgagtaac gcgtgaggaa 120cctgcctcaa
agagggggac aacagttgga aacgactgct aataccgcat aagcccacgg
180gtcggcatcg accagaggga aaaggagcaa tccgctttga gatggcctcg
cgtccgatta 240gctagttggt gaggtaatgg cccaccaagg caacgatcgg
tagccggact gagaggttga 300acggccacat tgggactgag acgcggccca
gactcctacg ggaggcagca gtggggaata 360ttgcacaatg ggggaaaccc
tgatgcagcg acgccgcgtg gaggaagaag gtcttcggat 420tgtaaactcc
tgttgttggg gaagataatg acggtaccca acaaggaagt gacggctaac
480tacgtgccag cagccgcggt aaaacgtagg tcacaagcgt tgtccggaat
tactgggtgt 540aaagggagcg caggcgggaa gacaagttgg aagtgaaatc
tatgggctca acccataaac 600tgctttcaaa actgtttttc ttgagtagtg
cagaggtagg cggaattccc ggtgtagcgg 660tggaatgcgt agatatcggg
aggaacacca gtggcgaagg cggcctactg ggcaccaact 720gacgctgagg
ctcgaaagtg tgggtagcaa acaggattag ataccctggt agtccacacc
780gtaaacgatg gttactaggt gttggaggat tgaccccttc agtgccgcag
ttaacacaat 840aagtaatcca cctggggagt acgaccgcaa ggttgaaact
caaaggaatt gacgggggcc 900cgcacaagca gtggagtatg tggtttaatt
cgacgcaacg cgaagaacct taccaagtct 960tgacatccct tgacagacat
agaaatatgt aatctcttcg gagcaaggag acaggtggtg 1020catggttgtc
gtcagctcgt gtcgtgagat gttgggttaa gtcccgcaac gagcgcaacc
1080cttatggtca gttactacgc aagaggactc tggccagact gccgttgaca
aaacggagga 1140aggtggggat gacgtcaaat catcatgccc tttatgactt
gggctacaca cgtactacaa 1200tggcgttaaa caaagagaag caagaccgcg
aggtggagca aaactcagaa acaacgtccc 1260agttcggact gcaggctgca
actcgcctgc acgaagtcgg aattgctagt aatcgtggat 1320cagcatgcca
cggtgaatac gttcccgggc cttgtacaca ccgcccgtca caccatgaga
1380gccgggggga cccgaagtcg gtagtctaac cgcaaggagg acgccgccga
aggtaaaact 1440ggtgattggg gtgaagtcgt aacaaggtag ccgt
147431408DNAFaecalibacterium prausnitzii 3gcgagagaga gcttgctttc
tcgagcgagt ggcgaacggg tgagtaacgc gtgaggaacc 60tgcctcaaag agggggacaa
cagttggaaa cgactgctaa taccgcataa gcccacggcc 120cggcatcggg
cagagggaaa aggagcaatc cgctttgaga tggcctcgcg tccgattagc
180tagttggtga ggtaacggcc caccaaggcg acgatcggta gccggactga
gaggttgaac 240ggccacattg ggactgagac acggcccaga ctcctacggg
aggcagcagt ggggaatatt 300gcacaatggg ggaaaccctg atgcagcgac
gccgcgtgga ggaagaaggt cttcggattg 360taaactcctg ttgttgagga
agataatgac ggtactcaac aaggaagtga cggctaacta 420cgtgccagca
gccgcggtaa aacgtaggtc acaagcgttg tccggaatta ctgggtgtaa
480agggagcgca ggcgggaaga caagttggaa gtgaaatcca tgggctcaac
ccatgaactg 540ctttcaaaac tgtttttctt gagtagtgca gaggtaggcg
gaattcccgg tgtagcggtg 600gaatgcgtag atatcgggag gaacaccagt
ggcgaaggcg gcctactggg caccaactga 660cgctgaggct cgaaagtgtg
ggtagcaaac aggattagat accctggtag tccacaccgt 720aaacgatgat
tactaggtgt tggaggattg accccttcag tgccgcagtt aacacaataa
780gtaatccacc tggggagtac gaccgcaagg ttgaaactca aaggaattga
cgggggcccg 840cacaagcagt ggagtatgtg gtttaattcg acgcaacgcg
aagaacctta ccaagtcttg 900acatcctgcg acggttctgg aaacagaact
ttccttcggg acgcagagac aggtggtgca 960tggttgtcgt cagctcgtgt
cgtgagatgt tgggttaagt cccgcaacga gcgcaaccct 1020tatggtcagt
tactacgcaa gaggactctg gccagactgc cgttgacaaa acggaggaag
1080gtggggatga cgtcaaatca tcatgccctt tatgacttgg gctacacacg
tactacaatg 1140gcgttaaaca aagagaagca agaccgcgag gtggagcaaa
actcagaaac aacgtcccag 1200ttcggactgc aggctgcaac tcgcctgcac
gaagtcggaa ttgctagtaa tcgtggatca 1260gcatgccacg gtgaatacgt
tcccgggcct tgtacacacc gcccgtcaca ccatgagagc 1320cggggggacc
cgaagtcggt agtctaaccg caaggaggac gccgccgaag gtaaaactgg
1380tgattggggt gaagtcgtaa caaggtag 140841405DNAFaecalibacterium
prausnitzii 4agcgagagag agcttgcttt ctcgagcgag tggcgaacgg gtgagtaacg
cgtgaggaac 60ctgcctcaaa gagggggaca acagttggaa acgactgcta ataccgcata
agcccacggt 120gccgcatggc acagagggaa aaggagcaat ccgctttgag
atggcctcgc gtccgattag 180ctagttggtg aggtaacggc ccaccaaggc
gacgatcggt agccggactg agaggttgaa 240cggccacatt gggactgaga
cacggcccag actcctacgg gaggcagcag tggggaatat 300tgcacaatgg
gggaaaccct gatgcagcga cgccgcgtgg aggaagaagg tcttcggatt
360gtaaactcct gttgttgggg aagataatga cggtacccaa caaggaagtg
acggctaact 420acgtgccagc agccgcggta aaacgtaggt cacaagcgtt
gtccggaatt actgggtgta 480aagggagcgc aggcgggaag acaagttgga
agtgaaatct atgggctcaa cccataaact 540gctttcaaaa ctgtttttct
tgagtagtgc agaggtaggc ggaattcccg gtgtagcggt 600ggaatgcgta
gatatcggga ggaacaccag tggcgaaggc ggcctactgg gcaccaactg
660acgctgaggc tcgaaagtgt gggtagcaaa caggattaga taccctggta
gtccacaccg 720taaacgatga ttactaggtg ttggaggatt gaccccttca
gtgccgcagt taacacaata 780agtaatccac ctggggagta cgaccgcaag
gttgaaactc aaaggaattg acgggggccc 840gcacaagcag tggagtatgt
ggtttaattc gacgcaacgc gaagaacctt accaagtctt 900gacatccctt
gacaggcata gaaatatgtt ttctcttcgg agcaaggaga caggtggtgc
960atggttgtcg tcagctcgtg tcgtgagatg ttgggttaag tcccgcaacg
agcgcaaccc 1020ttatggtcag ttactacgca agaggactct ggccagactg
ccgttgacaa aacggaggaa 1080ggtggggatg acgtcaaatc atcatgccct
ttatgacttg ggctacacac gtactacaat 1140ggcgttaaac aaagagaagc
aagaccgcga ggtggagcaa aactcagaaa caacgtccca 1200gttcggactg
caggctgcaa ctcgcctgca cgaagtcgga attgctagta atcgtggatc
1260agcatgccac ggtgaatacg ttcccgggcc ttgtacacac cgcccgtcac
accatgagag 1320ccggggggac ccgaagtcgg tagtctaacc gcaaggagga
cgccgccgaa ggtaaaactg 1380gtgattgggg tgaagtcgta acaag
140551385DNAFaecalibacterium prausnitzii 5cgagtggcga acgggtgagt
aacgcgtgag gaacctgcct caaagagggg gacaacagtt 60ggaaacgact gctaataccg
cataagccca caggtcggca tcgaccagag ggaaaaggag 120caatccgctt
tgagatggcc tcgcgtccga ttagctagtt ggtgaggtaa tggcccacca
180aggcaacgat cggtagccgg actgagaggt tgaacggcca cattgggact
gagacacggc 240ccagactcct acgggaggca gcagtgggga atattgcaca
atgggggaaa ccctgatgca 300gcgacgccgc gtggaggaag aaggtcttcg
gattgtaaac tcctgttgtt gaggaagata 360atgacggtac tcaacaagga
agtgacggct aactacgtgc cagcagccgc ggtaaaacgt 420aggtcacaag
cgttgtccgg aattactggg tgtaaaggga gcgcaggcgg gaagacaagt
480tggaagtgaa atctatgggc tcaacccata aactgctttc aaaactgttt
ttcttgagta 540gtgcagaggt aggcggaatt cccggtgtag cggtggaatg
cgtagatatc gggaggaaca 600ccagtggcga aggcggccta ctgggcacca
actgacgctg aggctcgaaa gtgtgggtag 660caaacaggat tagataccct
ggtagtccac accgtaaacg atgattacta ggtgttggag 720gattgacccc
ttcagtgccg cagttaacac aataagtaat ccacctgggg agtacgaccg
780caaggttgaa actcaaagga attgacgggg gcccgcacaa gcagtggagt
atgtggttta 840attcgacgca acgcgaagaa ccttaccaag tcttgacatc
ctgtgacgat gctggaaaca 900tgtttttcct tcggaacgca gagacaggtg
gtgcatggtt gtcgtcagct cgtgtcgtga 960gatgttgggt taagtcccgc
aacgagcgca acccttactg tcagttacta cgcaagagga 1020ctctggcagg
actgccgttg acaaaacgga ggaaggtggg gatgacgtca aatcatcatg
1080ccctttatga cttgggctac acacgtacta caatggcgtt aaacaaagag
aagcaagacc 1140gcgaggtgga gcaaaactca gaaacaacgt cccagttcgg
actgcaggct gcaactcgcc 1200tgcacgaagt cggaattgct agtaatcgtg
gatcagcatg ccacggtgaa tacgttcccg 1260ggccttgtac acaccgcccg
tcacaccatg agagccgggg ggacccgaag tcggtagtct 1320aaccgcaagg
aggacgccgc cgaaggtaaa actggtgatt ggggtgaagt cgtaacaagg 1380tagcc
138561405DNAFaecalibacterium prausnitzii 6cgagcgagag agagcttgct
ttctcaatcg agtggcgaac gggtgagtaa cgcgtgagga 60acctgcctca aagaggggga
caacagttgg aaacgactgc taataccgca taagcccaca 120ggtcggcatc
gaccagaggg aaaaggagca atccgctttg agatggcctc gcgtccgatt
180agctagttgg tgaggtaatg gcccaccaag gcaacgatcg gtagccggac
tgagaggttg 240aacggccaca ttgggactga gacacggccc agactcctac
gggaggcagc agtggggaat 300attgcacaat gggggaaacc ctgatgcagc
gacgccgcgt ggaggaagaa ggtcttcgga 360ttgtaaactc ctgttgttga
ggaagataat gacggtactc aacaaggaag tgacggctaa 420ctacgtgcca
gcagccgcgg taaaacgtag gtcacaagcg ttgtccggaa ttactgggtg
480taaagggagc gcaggcggga agacaagttg gaagtgaaat ctatgggctc
aacccataaa 540ctgctttcaa aactgttttt cttgagtagt gcagaggtag
gcggaattcc cggtgtagcg 600gtggaatgcg tagatatcgg gaggaacacc
agtggcgaag gcggcctact gggcaccaac 660tgacgctgag gctcgaaagt
gtgggtagca aacaggatta gataccctgg tagtccacac 720cgtaaacgat
gattactagg tgttggagga ttgacccctt cagtgccgca gttaacacaa
780taagtaatcc acctggggag tacgaccgca aggttgaaac tcaaaggaat
tgacgggggc 840ccgcacaagc agtggagtat gtggtttaat tcgacgcaac
gcgaagaacc ttaccaagtc 900ttgacatcct gtgacgaacc tggaaatatg
tttttccttc ggaacgcaga gacaggtggt 960gcatggttgt cgtcagctcg
tgtcgtgaga tgttgggtta agtcccgcaa cgagcgcaac 1020ccttactgtc
agttactacg caagaggact ctggcaggac tgccgttgac aaaacggagg
1080aaggtgggga tgacgtcaaa tcatcatgcc ctttatgact tgggctacac
acgtactaca 1140atggcgttaa acaaagagaa gcaagaccgc gaggtggagc
aaaactcaga aacaacgtcc 1200cagttcggac tgcaggctgc aactcgcctg
cacgaagtcg gaattgctag taatcgtgga 1260tcagcatgcc acggtgaata
cgttcccggg ccttgtacac accgcccgtc acaccatgag 1320agccgggggg
acccgaagtc ggtagtctaa ccgcaaggag gacgccgccg aaggtaaaac
1380tggtgattgg ggtgaagtcg tacag 140571474DNAFaecalibacterium
prausnitzii 7agagtttgat cctggctcag gacgaacgct ggcggcgcgc ctaacacatg
caagtcgaac 60gagcgagaga gagcttgctt tctcgagcga gtggcgaacg ggtgagtaac
gcgtggggaa 120cctgcctcaa agagggggac aacagttgga aacgactgct
aataccgcat aagcccacga 180cctggcatcg ggttgaggga aaaggagcaa
tccgctttga gatggcctcg cgtccgatta 240gctagttggt gaggtaatgg
cccaccaagg caacgatcgg tagccggact gagaggttga 300acggccacat
tgggactgag acacggccca gactcctacg ggaggcagca gtggggaata
360ttgcacaatg ggggaaaccc tgatgcagcg acgccgcgtg gaggaagaag
gtcttcggat 420tgtaaactcc tgttgttgag gaagataatg acggtactca
acaaggaagt gacggctaac 480tacgtgccag cagccgcggt aaaacgtagg
tcacaagcgt tgtccggaat tactgggtgt 540aaagggagcg caggcgggaa
gacaagttgg aagtgaaatc catgggctca acccatgaac 600tgctttcaaa
actgtttttc ttgagtagtg cagaggtagg cggaattccc ggtgtagcgg
660tggaatgcgt agatatcggg aggaacacca gtggcgaagg cggcctactg
ggcaccaact 720gacgctgagg ctcgaaagtg tgggtagcaa acaggattag
ataccctggt agtccacacc 780gtaaacgatg attactaggt gttggaggat
tgaccccttc agtgccgcag ttaacacaat 840aagtaatcca cctggggagt
acgaccgcaa ggttgaaact caaaggaatt gacgggggcc 900cgcacaagca
gtggagtatg tggtttaatt cgacgcaacg cgaagaacct taccaagtct
960tgacatcctg cgacggtgct ggaaacagtg ctttccttcg ggacgcagag
acaggtggtg 1020catggttgtc gtcagctcgt gtcgtgagat gttgggttaa
gtcccgcaac gagcgcaacc 1080cttatggtca gttactacgc aagaggactc
tggccagact gccgttgaca aaacggagga 1140aggtggggat gacgtcaaat
catcatgccc tttatgactt gggctacaca cgtactacaa 1200tggcgttaaa
caaagagaag caagaccgcg aggtggagca aaactcagaa acaacgtccc
1260agttcggact gcaggctgca actcgcctgc acgaagtcgg aattgctagt
aatcgtggat 1320cagcatgcca cggtgaatac gttcccgggc cttgtacaca
ccgcccgtca caccatgaga 1380gccgggggga cccgaagtcg gtagtctaac
cgcaaggagg acgccgccga aggtaaaact 1440ggtgattggg gtgaagtcgt
aacaaggtag ccgt 147481533DNAFaecalibacterium prausnitzii
8gcatgctcga gcggccgcca gtgtgatgga tatctgcaga attcgccctt agagtttgat
60cctggctcag gacgaacgct ggcggcgcgc ctaacacatg caagtcgaac gagcgagaga
120gagcttgctt tctcgagcga gtggcgaacg ggtgagtaac gcgtgaggaa
cctgcctcaa 180agagggggac aacagttgga aacgactgct aataccgcat
aagcccacga cccggcatcg 240ggtagaggga aaaggagcaa tccgctttga
gatggcctcg cgtccgatta gctagttggt 300gaggtaacgg cccaccaagg
cgacgatcgg tagccggact gagaggttga acggccacat 360tgggactgag
acacggccca gactcctacg ggaggcagca gtggggaata ttgcacaatg
420ggggaaaccc tgatgcagcg acgccgcgtg gaggaagaag gtcttcggat
tgtaaactcc 480tgttgttgag gaagataatg acggtactca acaaggaagt
gacggctaac tacgtgccag 540cagccgcggt aaaacgtagg tcacaagcgt
tgtccggaat tactgggtgt aaagggagcg 600caggcgggaa gacaagttgg
aagtgaaatc catgggctca acccatgaac tgctttcaaa 660actgtttttc
ttgagtagtg cagaggtagg cggaattccc ggtgtagcgg tggaatgcgt
720agatatcggg aggaacacca gtggcgaagg cggcctactg ggcaccaact
gacgctgagg 780ctcgaaagtg tgggtagcaa acaggattag ataccctggt
agtccacacc gtaaacgatg 840attactaggt gttggaggat tgaccccttc
agtgccgcag ttaacacaat aagtaatcca 900cctggggagt acgaccgcaa
ggttgaaact caaaggaatt gacgggggcc cgcacaagca 960gtggagtatg
tggtttaatt cgacgcaacg cgaagaacct taccaagtct tgacatcctg
1020cgacggttct ggaaacagaa ctttccttcg ggacgcagag acaggtggtg
catggttgtc 1080gtcagctcgt gtcgtgagat gttgggttaa gtcccgcaac
gagcgcaacc cttatggtca 1140gttactacgc aagaggactc tggccagact
gccgttgaca aaacggagga aggtggggat 1200gacgtcaaat catcatgccc
tttatgactt gggctacaca cgtactacaa tggcgttaaa 1260caaagagaag
caagaccgcg aggtggagca aaactcagaa acaacgtccc agttcggact
1320gcaggctgca actcgcctgc acgaagtcgg aattgctagt aatcgtggat
cagcatgcca 1380cggtgaatac gttcccgggc cttgtacaca ccgcccgtca
caccatgaga gccgggggga 1440cccgaagtcg gtagtctaac cgcaaggagg
acgccgccga aggtaaaact ggtgattggg 1500gtgaagtcgt aacaaggtag
ccgtaagggc gaa 153391286DNAFaecalibacterium prausnitzii 9gcatcgggca
gagggaaaag gagcaatccg ctttgagatg gcctcgcgtc cgattagcta 60gttggtgagg
taatggccca ccaaggcgac gatcggtagc cggactgaga ggttgaacgg
120ccacattggg actgagacac ggcccagact cctacgggag gcagcagtgg
ggaatattgc 180acaatggggg aaaccctgat gcagcgacgc cgcgtggagg
aagaaggtct tcggattgta 240aactcctgtt gttgaggaag ataatgacgg
tactcaacaa ggaagtgacg gctaactacg 300tgccagcagc cgcggtaaaa
cgtaggtcac aagcgttgtc cggaattact gggtgtaaag 360ggagcgcagg
cgggaagaca agttggaagt gaaatccatg ggctcaaccc atgaactgct
420ttcaaaactg tttttcttga gtagtgcaga ggtaggcgga attcccggtg
tagcggtgga 480atgcgtagat atcgggagga acaccagtgg cgaaggcggc
ctactgggca ccaactgacg 540ctgaggctcg aaagtgtggg tagcaaacag
gattagatac cctggtagtc cacactgtaa 600acgatgatta ctaggtgttg
gaggattgac cccttcagtg ccgcagttaa cacaataagt 660aatccacctg
gggagtacga ccgcaaggtt gaaactcaaa ggaattgacg ggggcccgca
720caagcagtgg agtatgtggt ttaattcgac gcaacgcgaa gaaccttacc
aagtcttgac 780atcctgcgac gcacatagaa atatgtgttt ccttcgggac
gcagagacag gtggtgcatg 840gttgtcgtca gctcgtgtcg tgagatgttg
ggttaagtcc cgcaacgagc gcaaccctta 900tggtcagtta ctacgcaaga
ggactctggc cagactgccg ttgacaaaac ggaggaaggt 960ggggatgacg
tcaaatcatc atgcccttta tgacttgggc tacacacgta ctacaatggc
1020gttaaacaaa gagaagcaag accgcgaggt ggagcaaaac tcagaaacaa
cgtcccagtt 1080cggactgcag gctgcaactc gcctgcacga agtcggaatt
gctagtaatc gcagatcagc 1140atgctgcggt gaatacgttc ccgggccttg
tacacaccgc ccgtcacacc atgagagccg 1200gggggacccg aagtcggtag
tctaaccgca aggaggacgc cgccgaaggt aaaactggtg 1260attggggtga
agtcgtaaca aggtag 1286101407DNAFaecalibacterium prausnitzii
10cgagcgagag agagcttgct ttctcgagcg agtggcgaac gggtgagtaa cgcgtgagga
60acctgcctca aagaggggga caacagttgg aaacgactgc taataccgca taagcccacg
120ggtcggcatc gaccagaggg aaaaggagca atccgctttg agatggcctc
gcgtccgatt 180agctagttgg tgaggtaacg gcccaccaag gcaacgatcg
gtagccggac tgagaggttg 240aacggccaca ttgggactga gacacggccc
agactcctac gggaggcagc agtggggaat 300attgcacaat gggggaaacc
ctgatgcagc gacgccgcgt ggaggaagaa ggtcttcgga 360ttgtaaactc
ctgttgttgg ggaagataat gacggtaccc aacaaggaag tgacggctaa
420ctacgtgcca gcagccgcgg taaaacgtag gtcacaagcg ttgtccggaa
ttactgggtg 480taaagggagc gcaggcggga agacaagttg gaagtgaaat
ctatgggctc aacccataaa 540ctgctttcaa aactgttttt cttgagtagt
gcagaggtag gcggaattcc cggtgtagcg 600gtggaatgcg tagatatcgg
gaggaacacc agtggcgaag gcggcctact gggcaccaac 660tgacgctgag
gctcgaaagt gtgggtagca aacaggatta gataccctgg tagtccacac
720cgtaaacgat gattactagg tgttggagga ttgacccctt cagtgccgca
gttaacacaa 780taagtaatcc acctggggag tacgaccgca aggttgaaac
tcaaaggaat tgacgggggc 840ccgcacaagc agtggagtat gtggtttaat
tcgacgcaac gcgaagaacc ttaccaagtc 900ttgacatccc ttgacagaca
tagaaatatg taatctcttc ggagcaagga gacaggtggt 960gcatggttgt
cgtcagctcg tgtcgtgaga tgttgggtta agtcccgcaa cgagcgcaac
1020ccttatggtc agttactacg caagaggact ctggccagac tgccgttgac
aaaacggagg 1080aaggtgggga tgacgtcaaa tcatcatgcc ctttatgact
tgggctacac acgtactaca 1140atggcgttaa acaaagagaa gcaagaccgc
gaggtggagc aaaactcaga aacaacgtcc 1200cagttcggac tgcaggctgc
aactcgcctg cacgaagtcg gaattgctag taatcgtgga 1260tcagcatgcc
acggtgaata cgttcccggg ccttgtacac accgcccgtc acaccatgag
1320agccgggggg acccgaagtc ggtagtctaa ccgcaaggag gacgccgccg
aaggtaaaac 1380tggtgattgg ggtgaagtcg taacaag
1407111382DNAFaecalibacterium prausnitzii 11gagcgagtgg cgaacgggtg
agtaacgcgt gaggaacctg cctcaaagag ggggacaaca 60gttggaaacg actgctaata
ccgcataagc ccacgacccg gcatcgggta gagggaaaag 120gagcaatccg
ctttgagatg gcctcgcgtc cgattagcta gttggtgagg taatggccca
180ccaaggcgac gatcggtagc cggactgaga ggttgaacgg ccacattggg
actgagacac 240ggcccagact cctacgggag gcagcagtgg ggaatattgc
acaatggggg aaaccctgat 300gcagcgacgc cgcgtggagg aagaaggtct
tcggattgta aactcctgtt gttgaggaag 360ataatgacgg tactcaacaa
ggaagtgacg gctaactacg tgccagcagc cgcggtaaaa 420cgtaggtcac
aagcgttgtc cggaattact gggtgtaaag ggagcgcagg cgggaagaca
480agttggaagt gaaatccatg ggctcaaccc atgaactgct ttcaaaactg
tttttcttga 540gtagtgcaga ggtaggcgga attcccggtg tagcggtgga
atgcgtagat atcgggagga 600acaccagtgg cgaaggcggc ctactgggca
ccaactgacg ctgaggctcg aaagtgtggg 660tagcaaacag gattagatac
cctggtagtc cacactgtaa acgatgatta ctaggtgttg 720gaggattgac
cccttcagtg ccgcagttaa cacaataagt aatccacctg gggagtacga
780ccgcaaggtt gaaactcaaa ggaattgacg ggggcccgca caagcagtgg
agtatgtggt 840ttaattcgac gcaacgcgaa gaaccttacc aagtcttgac
atcctgcgac gcacatagaa 900atatgtgttt ccttcgggac gcagagacag
gtggtgcatg gttgtcgtca gctcgtgtcg 960tgagatgttg ggttaagtcc
cgcaacgagc gcaaccctta tggtcagtta ctacgcaaga 1020ggactctggc
cagactgccg ttgacaaaac ggaggaaggt ggggatgacg tcaaatcatc
1080atgcccttta tgacttgggc tacacacgta ctacaatggc gttaaacaaa
gagaagcaag 1140accgcgaggt ggagcaaaac tcagaaacaa cgtcccagtt
cggactgcag gctgcaactc 1200gcctgcacga agtcggaatt gctagtaatc
gcagatcagc atgctgcggt gaatacgttc 1260ccgggccttg tacacaccgc
ccgtcacacc atgagagccg gggggacccg aagtcggtag 1320tctaaccgca
aggaggacgc cgccgaaggt aaaactggtg attggggtga agtcgtaaca 1380ag
1382121395DNAFaecalibacterium prausnitzii 12agcttgcttt ctcgagcgag
tggcgaacgg gtgagtaacg cgtgaggaac ctgcctcaaa 60gagggggaca acagttggaa
acgactgcta ataccgcata agcccacggg tcggcatcga 120ccagagggaa
aaggagcaat ccgctttgag atggcctcgc gtccgattag ctagttggtg
180aggtaacggc ccaccaaggc gacgatcggt agccggactg agaggttgaa
cggccacatt 240gggactgaga cacggcccag actcctacgg gaggcagcag
tggggaatat tgcacaatgg 300gggaaaccct gatgcagcga cgccgcgtgg
aggaagaagg tcttcggatt gtaaactcct 360gttgttgggg aagataatga
cggtacccaa caaggaagtg acggctaact acgtgccagc 420agccgcggta
aaacgtaggt cacaagcgtt gtccggaatt actgggtgta aagggagcgc
480aggcgggaag acaagttgga agtgaaatct atgggctcaa cccataaact
gctttcaaaa 540ctgtttttct tgagtagtgc agaggtaggc ggaattcccg
gtgtagcggt ggaatgcgta 600gatatcggga ggaacaccag tggcgaaggc
ggcctactgg gcaccaactg acgctgaggc 660tcgaaagtgt gggtagcaaa
caggattaga taccctggta gtccacaccg taaacgatga 720ttactaggtg
ttggaggatt gaccccttca gtgccgcagt taacacaata agtaatccac
780ctggggagta cgaccgcaag gttgaaactc aaaggaattg acgggggccc
gcacaagcag 840tggagtatgt ggtttaattc gacgcaacgc gaagaacctt
accaagtctt gacatccctt 900gacagacata gaaatatgta ttctcttcgg
agcaaggaga caggtggtgc atggttgtcg 960tcagctcgtg tcgtgagatg
ttgggttaag tcccgcaacg agcgcaaccc ttatggtcag 1020ttactacgca
agaggactct ggccagactg ccgttgacaa aacggaggaa ggtggggatg
1080acgtcaaatc atcatgccct ttatgacttg ggctacacac gtactacaat
ggcgttaaac 1140aaagagaagc aagaccgcga ggtggagcaa aactcagaaa
caacgtccca gttcggactg 1200caggctgcaa ctcgcctgca cgaagtcgga
attgctagta atcgtggatc agcatgccac 1260ggtgaatacg ttcccgggcc
ttgtacacac cgcccgtcac accatgagag ccggggggac 1320ccgaagtcgg
tagtctaacc gcaaggagga cgccgccgaa ggtaaaactg gtgattgggg
1380tgaagtcgta acaag 1395131390DNAFaecalibacterium prausnitzii
13atcgagtggc gaacgggtga gtaacgcgtg aggaacctgc ctcaaagagg gggacaacag
60ttggaaacga ctgctaatac cgcataagcc cacggctcgg catcgagcag agggaaaagg
120agcaatccgc tttgagatgg cctcgcgtcc gattagctag ttggtgaggt
aatggcccac 180caaggcgacg atcggtagcc ggactgagag gttgaacggc
cacattggga ctgagacacg 240gcccagactc ctacgggagg cagcagtggg
gaatattgca caatggggga aaccctgatg 300cagcgacgcc gcgtggagga
agaaggtctt cggattgtaa actcctgttg ttgaggaaga 360taatgacggt
actcaacaag gaagtgacgg ctaactacgt gccagcagcc gcggtaaaac
420gtaggtcaca agcgttgtcc ggaattactg ggtgtaaagg gagcgcaggc
gggcgatcaa 480gttggaagtg aaatccatgg gctcaaccca tgaactgctt
tcaaaactga ttgtcttgag 540tagtgcagag gtaggcggaa ttcccggtgt
agcggtggaa tgcgtagata tcgggaggaa 600caccagtggc gaaggcggcc
tactgggcac caactgacgc tgaggctcga aagtgtgggt 660agcaaacagg
attagatacc ctggtagtcc acaccgtaaa cgatgattac taggtgttgg
720aggattgacc ccttcagtgc cgcagttaac acaataagta atccacctgg
ggagtacgac 780cgcaaggttg aaactcaaag gaattgacgg gggcccgcac
aagcagtgga gtatgtggtt 840taattcgacg caacgcgaag aaccttacca
agtcttgaca tcctgcgacg atgctagaaa 900tagtattttc cttcgggacg
cagagacagg tggtgcatgg ttgtcgtcag ctcgtgtcgt 960gagatgttgg
gttaagtccc gcaacgagcg caacccttat ggtcagttac tacgcaagag
1020gactctggcc agactgccgt tgacaaaacg gaggaaggtg gggatgacgt
caaatcatca 1080tgccctttat gacttgggct acacacgtac tacaatggcg
ttaaacaaag agaagcaaga 1140ccgcgaggtg gagcaaaact cagaaacaac
gtcccagttc ggactgcagg ctgcaactcg 1200cctgcacgaa gtcggaattg
ctagtaatcg cagatcagca tgctgcggtg aatacgttcc 1260cgggccttgt
acacaccgcc cgtcacacca tgagagccgg ggggacccga agtcggtagt
1320ctaaccgcaa ggaggacgcc gccgaaggta aaactggtga ttggggtgaa
gtcgtaacaa 1380ggtagccgtc 1390141400DNAFaecalibacterium prausnitzii
14gagagagctt gctttctcaa gcgagtggcg aacgggtgag taacgcgtga ggaacctgcc
60tcaaagaggg ggacaacagt tggaaacgac tgctaatacc gcataagccc acgacccggc
120atcgggtaga gggaaaagga gcaatccgct ttgagatggc ctcgcgtccg
attagctagt 180tggtgaggta acggcccacc aaggcgacga tcggtagccg
gactgagagg ttgaacggcc 240acattgggac tgagacacgg cccagactcc
tacgggaggc agcagtgggg aatattgcac 300aatgggggaa accctgatgc
agcgacgccg cgtggaggaa gaaggtcttc ggattgtaaa 360ctcctgttgt
tgaggaagat aatgacggta ctcaacaagg aagtgacggc taactacgtg
420ccagcagccg cggtaaaacg taggtcacaa gcgttgtccg gaattactgg
gtgtaaaggg 480agcgcaggcg ggaagacaag ttggaagtga aatccatggg
ctcaacccat gaactgcttt 540caaaactgtt tttcttgagt agtgcagagg
taggcggaat tcccggtgta gcggtggaat 600gcgtagatat cgggaggaac
accagtggcg aaggcggcct actgggcacc aactgacgct 660gaggctcgaa
agtgtgggta gcaaacagga ttagataccc tggtagtcca cactgtaaac
720gatgattact aggtgttgga ggattgaccc cttcagtgcc gcagttaaca
caataagtaa 780tccacctggg gagtacgacc gcaaggttga aactcaaagg
aattgacggg ggcccgcaca 840agcagtggag tatgtggttt aattcgacgc
aacgcgaaga accttaccaa gtcttgacat 900cctgcgacgg tgctggaaac
agtgctttcc ttcgggacgc agagacaggt ggtgcatggt 960tgtcgtcagc
tcgtgtcgtg agatgttggg ttaagtcccg caacgagcgc aacccttatg
1020gtcagttact acgcaagagg actctggcca gactgccgtt gacaaaacgg
aggaaggtgg 1080ggatgacgtc aaatcatcat gccctttatg acttgggcta
cacacgtact acaatggcgt 1140taaacaaaga gaagcaagac cgcgaggtgg
agcaaaactc agaaacaacg tcccagttcg 1200gactgcaggc tgcaactcgc
ctgcacgaag tcggaattgc tagtaatcgc agatcagcat 1260gctgcggtga
atacgttccc gggccttgta cacaccgccc gtcacaccat gagagccggg
1320gggacccgaa gtcggtagtc taaccgcaag gaggacgccg ccgaaggtaa
aactggtgat 1380tggggtgaag tcgtaacaag 1400151388DNAFaecalibacterium
prausnitzii 15caagcgagtg gcgaacgggt gagtaacgcg tgaggaacct
gcctcaaaga gggggacaac 60agttggaaac gactgctaat accgcataag cccacgaccc
ggcatcgggt agagggaaaa 120ggagcaatcc gctttgagat ggcctcgcgt
ccgattagct agttggtgag gtaacggccc 180accaaggcga cgatcggtag
ccggactgag aggttgaacg gccacattgg gactgagaca 240cggcccagac
tcctacggga ggcagcagtg gggaatattg cacaatgggg gaaaccctga
300tgcagcgacg ccgcgtggag gaagaaggtc ttcggattgt aaactcctgt
tgttgaggaa 360gataatgacg gtactcaaca aggaagtgac ggctaactac
gtgccagcag ccgcggtaaa 420acgtaggtca caagcgttgt ccggaattac
tgggtgtaaa gggagcgcag gcgggaagac 480aagttggaag tgaaatccat
gggctcaacc catgaactgc tttcaaaact gtttttcttg 540agtagtgcag
aggtaggcgg aattcccggt gtagcggtgg aatgcgtaga tatcgggagg
600aacaccagtg gcgaaggcgg cctactgggc accaactgac gctgaggctc
gaaagtgtgg 660gtagcaaaca ggattagata ccctggtagt ccacactgta
aacgatgatt actaggtgtt 720ggaggattga ccccttcagt gccgcagtta
acacaataag taatccacct ggggagtacg 780accgcaaggt tgaaactcaa
aggaattgac gggggcccgc acaagcagtg gagtatgtgg 840tttaattcga
cgcaacgcga agaaccttac caagtcttga catcctgcga cgcacataga
900aatatgtgtt tccttcggga cgcagagaca ggtggtgcat ggttgtcgtc
agctcgtgtc 960gtgagatgtt gggttaagtc ccgcaacgag cgcaaccctt
atggtcagtt actacgcaag 1020aggactctgg ccagactgcc gttgacaaaa
cggaggaagg tggggatgac gtcaaatcat 1080catgcccttt atgacttggg
ctacacacgt actacaatgg cgttaaacaa agagaagcaa 1140gaccgcgagg
tggagcaaaa ctcagaaaca acgtcccagt tcggactgca ggctgcaact
1200cgcctgcacg aagtcggaat tgctagtaat cgcagatcag catgctgcgg
tgaatacgtt 1260cccgggcctt gtacacaccg cccgtcacac catgagagcc
ggggggaccc gaagtcggta 1320gtctaaccgc aaggaggacg ccgccgaagg
taaaactggt gattggggtg aagtcgtaac 1380aagggtag
1388161474DNAFaecalibacterium prausnitzii 16agagtttgat cctggctcag
gacgaacgct ggcggcgcgc ctaacacatg caagtcgaac 60gagcgagaga gagcttgctt
tctcgagcga gtggcgaacg ggtgagtaac gcgtgaggaa 120cctgcctcaa
agagggggac aacagttgga aacgactgct aataccgcat aagcccacga
180cccggcatcg ggttgaggga aaaggagcaa tccgctttga gatggcctcg
cgtccgatta 240gctagttggt gaggtaacgg cccaccaagg cgacgatcgg
tagccggact gagaggttga 300acggccacat tgggactgag acacggccca
gactcctacg ggaggcagca gtggggaata 360ttgcacaatg ggggaaaccc
tgatgcagcg acgccgcgtg gaggaagaag gtcttcggat 420tgtaaactcc
tgttgttggg gaagataatg acggtaccca acaaggaagt gacggctaac
480tacgtgccag cagccgcggt aaaacgtagg tcacaagcgt tgtccggaat
tactgggtgt 540aaagggagcg caggcgggaa gacaagttgg aagtgaaatc
catgggctta acccatgaac 600tgctttcaaa actgtttttc ttgagtagtg
cagaggtagg cggaattccc ggtgtagcgg 660tggaatgcgt agatatcggg
aggaacacca gtggcgaagg cggcctactg ggcaccaact 720gacgctgagg
ctcgaaagtg tgggtagcaa acaggattag ataccctggt agtccacacc
780gtaaacgatg attactaggt gttggaggat tgaccccttc agtgccgcag
ttaacacaat 840aagtaatcca cctggggagt acgaccgcaa ggttgaaact
caaaggaatt gacgggggcc 900cgcacaagca gtggagtatg tggtttaatt
cgacgcaacg cgaagaacct taccaagtct 960tgacatcctg tgacagacgt
agaaatacgt tcttccttcg ggacacagag acaggtggtg 1020catggttgtc
gtcagctcgt gtcgtgagat gttgggttaa gtcccgcaac gagcgcaacc
1080cttatggtca gttactacgc aagaggactc tggccagact gccgttgaca
aaacggagga 1140aggtggggat gacgtcaaat catcatgccc tttatgactt
gggctacaca cgtactacaa 1200tggcgttaaa caaagagaag caagaccgcg
aggtggagca aaactcagaa acaacgtccc 1260agttcggact gcaggctgca
actcgcctgc acgaagtcgg aattgctagt aatcgtggat 1320cagcatgcca
cggtgaatac gttcccgggc cttgtacaca ccgcccgtca caccatgaga
1380gccgggggga cccgaagtcg gtagtctaac cgcaaggagg acgccgccga
aggtaaaact 1440ggtgattggg gtgaagtcgt aacaaggtag ccgt
1474171323DNAFaecalibacterium prausnitzii 17ttagtggcga acgggtgagt
aacgcgtgag taacctgccc tggagtgggg gacaacagtt 60ggaaacgact gctaataccg
cataagccca cggcccggca tcgggctgcg ggaaaaggat 120ttattcgctt
caggatggac tcgcgtccaa ttagctagtt ggtgaggtaa cggcccacca
180aggcgacgat tggtagccgg actgagaggt tgaacggcca cattgggact
gagacacggc 240ccagactcct acgggaggca gcagtggggg atattgcaca
atgggggaaa ccctgatgca 300gcgacgccgc gtggaggaag aaggttttcg
gattgtaaac tcctgtcgtt agggacgaat 360catgacggta cctaacaaga
aagcaccggc taactacgtg ccagcagccg cggtaaaacg 420tagggtgcaa
gcgttgtccg gaattactgg gtgtaaaggg agcgcaggcg gaccggcaag
480ttggaagtga aaaccatggg ctcaacccat gaattgcttt caaaactgct
ggccttgagt 540agtgcagagg taggtggaat tcccggtgta gcggtggaat
gcgtagatat cgggaggaac 600accagtggcg aaggcgacct actgggcacc
aactgacgct gaggctcgaa agcatgggta 660gcaaacagga ttagataccc
tggtagtcca tgccgtaaac gatgattact aggtgttgga 720ggattgaccc
cttcagtgcc gcagttaaca caataagtaa tccacctggg gagtacgacc
780gcaaggttga aactcaaagg aattgacggg ggcccgcaca agcagtggag
tatgtggttt 840aattcgaagc aacgcgaaga accttaccag gtcttgacat
ccgatgcata gtgcagagat 900gcatgaagtc cttcgggaca tcgagacagg
tggtgcatgg ttgtcgtcag ctcgtgtcgt 960gagatgttgg gttaagtccc
gcaacgagcg caacccttat tgccagttac tacgtaagag 1020gactctggcg
agactgccgt tgacaaaacg gaggaaggtg gggatgacgt caaatcatca
1080tgccctttat gacctgggct acacacgtac tacaatggcg tttaacaaag
agaagcaaga 1140ccgcgaggtg gagcaaaact cagaaacaac gtctcagttc
agattgcagg ctgcaactcg 1200cctgcatgaa gtcggaattg ctagtaatcg
cggatcagca tgccgcggtg aatacgttcc 1260cgggccttgt acacaccgcc
cgtcacacca tgagagccgg ggggacccga agtcggtagt 1320cta
1323181469DNAEubacterium desmolansmisc_feature(31)..(31)n is a, c,
g, t or umisc_feature(274)..(274)n is a, c, g, t or
umisc_feature(400)..(400)n is a, c, g, t or
umisc_feature(574)..(574)n is a, c, g, t or
umisc_feature(579)..(579)n is a, c, g, t or
umisc_feature(601)..(601)n is a, c, g, t or
umisc_feature(916)..(918)n is a, c, g, t or
umisc_feature(956)..(957)n is a, c, g, t or
umisc_feature(979)..(979)n is a, c, g, t or
umisc_feature(1016)..(1016)n is a, c, g, t or
umisc_feature(1025)..(1025)n is a, c, g, t or
umisc_feature(1038)..(1038)n is a, c, g, t or
umisc_feature(1079)..(1079)n is a, c, g, t or
umisc_feature(1179)..(1180)n is a, c, g, t or
umisc_feature(1195)..(1195)n is a, c, g, t or
umisc_feature(1373)..(1374)n is a, c, g, t or u 18tttttagaga
gtttgatcct ggctcaggat naacgctggc ggcgtgccta acacatgcaa 60gtcgaacgga
gttattttgg aaatctcttc ggagatggaa ttcataactt agtggcggac
120gggtgagtaa cgcgtgagca atctgccttt aggtggggga taacagtcgg
aaacggctgc 180taataccgca taatacgttt tgggggcatc cttgaaacgt
caaagattta ttgcctttag 240atgagctcgc gtctgattag ctggttggcg
gggnaacggc ccaccaaggc gacgatcagt 300agccggactg agaggttgaa
cggccacatt gggactgaga cacggcccag actcctacgg 360gaggcagcag
tggggaatat tgcgcaatgg gggaaacccn gacgcagcaa cgccgcgtga
420ttgaagaagg ccttcgggtt gtaaagatct ttaatcaggg acgaattttg
acggtacctg 480aagaataagc tccggctaac tacgtgccag cagccgcggt
aatacgtagg gagcaagcgt 540tatccggatt tactgggtgt aaagggcgcg
cagncgggnc ggcaagttgg gagtgaaatc 600ngggggctta acccccgaac
tgctttcaaa actgctggtc ttgagtgatg gagaggcagg 660cggaattccg
tgtgtagcgg tgaaatgcgt agatatacgg aggaacacca gtggcgaagg
720cggcctgctg gacattaact gacgctgagg cgcgaaagcg tggggagcaa
acaggattag 780ataccctggt agtccacgcc gtaaacgatg gatactaggt
gtgggaggta ttgacccctt 840ccgtgccgca gttaacacaa taagtatccc
acctggggag tacggccgca aggttgaaac 900tcaaaggaat tgacgnnngc
ccgcacaagc agtggagtat gtggtttaat tcgaannaac 960gcgaagaacc
ttaccaggnc ttgacatccc ggtgaccgtc ctagagatag gacttncctt
1020cgggncaacg gtgacagntg gtgcatggtt gtcgtcagct cgtgtcgtga
gatgttggnt 1080taagtcccgc aacgagcgca acccttacgg ttagttgata
cgcaagatca ctctagccgg 1140actgccgttg acaaaacgga ggaaggtggg
gacgacgtnn aatcatcatg ccccntatga 1200cctgggctac acacgtacta
caatggcagt catacagagg gaagcaaaat cgcgaggtgg 1260agcaaatccc
taaaagctgt cccagttcag attgcaggct gcaacccgcc tgcatgaagt
1320cggaattgct agtaatcgcg gatcagcatg ccgcggtgaa tacgttcccg
ggnnttgtac 1380acaccgcccg tcacaccatg agagccgtca atacccgaag
tccgtagcct aaccgcaagg 1440ggggcgcggc cgaaggtagg ggtggtaat 1469
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References