Abstract
The gut microbiota plays important roles in the development of the host immune system. We have previously shown that a combination of 46 strains of commensal Clostridia isolated from conventionally reared mice can induce the accumulation of CD4(+)Foxp3(+) regulatory T (Treg) cells in the mouse colonic lamina propria. Subsequently, we succeeded in isolating and selecting 17 strains of Clostridia from a healthy human fecal sample that can significantly increase the number and function of colonic Treg cells in colonized rodents, thereby attenuating symptoms of experimental allergic diarrhea and colitis. Here we characterize each of the 17 strains of human-derived Clostridia in terms of sensitivity to antibiotics and ability to produce short chain fatty acids and other metabolites, and discuss their potential as biotherapeutics to correct dysbiosis and treat immune-inflammatory diseases.
Keywords
Clostridia
Treg
gut microbiota
MeSH Terms
Animals
Anti-Bacterial Agents/pharmacology
Clostridium/drug effects,immunology,isolation & purification,physiology
Colon/microbiology
Cytosol/chemistry
Dysbiosis/therapy
Fatty Acids/analysis
Fatty Acids, Volatile/metabolism
Feces/microbiology
Healthy Volunteers
Humans
Mice
Microbial Sensitivity Tests
Probiotics/administration & dosage
Symbiosis
T-Lymphocytes, Regulatory/immunology
Chemicals
Anti-Bacterial Agents
Fatty Acids
Fatty Acids, Volatile
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Narushima Seiko
RIKEN Center for Integrative Medical Sciences (IMS-RCAI); Yokohama, Japan.
Sugiura Yuki
Department of Biochemistry; School of Medicine; Keio University; Tokyo, Japan; Japan Science and Technology Agency; Precursory Research for Embryonic Science and Technology (PRESTO); Kawaguchi, Japan.
Oshima Kenshiro
Graduate School of Frontier Sciences; The University of Tokyo; Kashiwa, Japan; Japan Science and Technology Agency; Core Research for Evolutional Science and Technology (CREST); Kawaguchi, Japan.
Atarashi Koji
RIKEN Center for Integrative Medical Sciences (IMS-RCAI); Yokohama, Japan; Japan Science and Technology Agency; Precursory Research for Embryonic Science and Technology (PRESTO); Kawaguchi, Japan.
Hattori Masahira
Graduate School of Frontier Sciences; The University of Tokyo; Kashiwa, Japan.
Suematsu Makoto
Department of Biochemistry; School of Medicine; Keio University; Tokyo, Japan; Japan Science and Technology Agency; Exploratory Research for Advanced Technology (ERATO); Suematsu Gas Biology Project; Tokyo, Japan.
Honda Kenya
RIKEN Center for Integrative Medical Sciences (IMS-RCAI); Yokohama, Japan; Japan Science and Technology Agency; Core Research for Evolutional Science and Technology (CREST); Kawaguchi, Japan.
References (28)
28 references, click to expand
-
Commensal bacteria-dependent indole production enhances epithelial barrier function in the colon.
PLoS One. 2013 Nov 20;8(11):e80604
PMID: 24278294
-
High-performance liquid chromatographic analysis of serum short-chain fatty acids by direct derivatization.
J Chromatogr. 1987 Oct 9;421(1):33-41
PMID: 3429573
-
Unbalance of intestinal microbiota in atopic children.
BMC Microbiol. 2012 Jun 06;12:95
PMID: 22672413
-
Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system.
Cell. 2007 Oct 5;131(1):33-45
PMID: 17923086
-
The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.
Science. 2013 Aug 2;341(6145):569-73
PMID: 23828891
-
The phylogeny of the genus Clostridium: proposal of five new genera and eleven new species combinations.
Int J Syst Bacteriol. 1994 Oct;44(4):812-26
PMID: 7981107
-
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation.
Nature. 2013 Dec 19;504(7480):451-5
PMID: 24226773
-
Comparison of three PCR primer sets for identification of vanB gene carriage in feces and correlation with carriage of vancomycin-resistant enterococci: interference by vanB-containing anaerobic bacilli.
Antimicrob Agents Chemother. 2005 Jan;49(1):77-81
PMID: 15616278
-
Duodenal infusion of donor feces for recurrent Clostridium difficile.
N Engl J Med. 2013 Jan 31;368(5):407-15
PMID: 23323867
-
Hypoxic regulation of the cerebral microcirculation is mediated by a carbon monoxide-sensitive hydrogen sulfide pathway.
Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1293-8
PMID: 22232681
-
Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases.
Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13780-5
PMID: 17699621
-
Therapeutic potential of fecal microbiota transplantation.
Gastroenterology. 2013 Nov;145(5):946-53
PMID: 24018052
-
Induction of intestinal Th17 cells by segmented filamentous bacteria.
Cell. 2009 Oct 30;139(3):485-98
PMID: 19836068
-
Suppression of Clostridium difficile in the gastrointestinal tracts of germfree mice inoculated with a murine isolate from the family Lachnospiraceae.
Infect Immun. 2012 Nov;80(11):3786-94
PMID: 22890996
-
Characterization of clostridia isolated from faeces of limited flora mice and their effect on caecal size when associated with germ-free mice.
Lab Anim. 1985 Apr;19(2):111-8
PMID: 3889493
-
The microbiome in infectious disease and inflammation.
Annu Rev Immunol. 2012;30:759-95
PMID: 22224764
-
Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota.
Nature. 2013 Aug 8;500(7461):232-6
PMID: 23842501
-
Probiotic bacteria influence the composition and function of the intestinal microbiota.
Interdiscip Perspect Infect Dis. 2008;2008:175285
PMID: 19277099
-
Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma.
EMBO Rep. 2012 May 01;13(5):440-7
PMID: 22422004
-
Intestinal commensal microbes as immune modulators.
Cell Host Microbe. 2012 Oct 18;12(4):496-508
PMID: 23084918
-
Identification and antimicrobial resistance patterns of clinical isolates of Clostridium clostridioforme, Clostridium innocuum, and Clostridium ramosum compared with those of clinical isolates of Clostridium perfringens.
J Clin Microbiol. 1995 Dec;33(12):3209-15
PMID: 8586704
-
Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach.
Gut. 2006 Feb;55(2):205-11
PMID: 16188921
-
Induction of colonic regulatory T cells by indigenous Clostridium species.
Science. 2011 Jan 21;331(6015):337-41
PMID: 21205640
-
Diversity of the autochthonous colonic microbiota.
Gut Microbes. 2011 Mar-Apr;2(2):99-104
PMID: 21694499
-
The microbiology of butyrate formation in the human colon.
FEMS Microbiol Lett. 2002 Dec 17;217(2):133-9
PMID: 12480096
-
Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine.
FEMS Microbiol Lett. 2009 May;294(1):1-8
PMID: 19222573
-
Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis.
Immunity. 2014 Jan 16;40(1):128-39
PMID: 24412617
-
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells.
Nature. 2013 Dec 19;504(7480):446-50
PMID: 24226770