Article (Scientific journals)
Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota
Atarshi, Koji; Tanoue, Takeshi; Oshima, Kenshiro et al.
2013In Nature, 500, p. 232-236
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Abstract :
[en] Manipulation of the gut microbiota holds great promise for the treatment of inflammatory and allergic diseases1, 2. Although numerous probiotic microorganisms have been identified3, there remains a compelling need to discover organisms that elicit more robust therapeutic responses, are compatible with the host, and can affect a specific arm of the host immune system in a well-controlled, physiological manner. Here we use a rational approach to isolate CD4+FOXP3+ regulatory T (Treg)-cell-inducing bacterial strains from the human indigenous microbiota. Starting with a healthy human faecal sample, a sequence of selection steps was applied to obtain mice colonized with human microbiota enriched in Treg-cell-inducing species. From these mice, we isolated and selected 17 strains of bacteria on the basis of their high potency in enhancing Treg cell abundance and inducing important anti-inflammatory molecules—including interleukin-10 (IL-) and inducible T-cell co-stimulator (ICOS)—in Treg cells upon inoculation into germ-free mice. Genome sequencing revealed that the 17 strains fall within clusters IV, XIVa and XVIII of Clostridia, which lack prominent toxins and virulence factors. The 17 strains act as a community to provide bacterial antigens and a TGF-β-rich environment to help expansion and differentiation of Treg cells. Oral administration of the combination of 17 strains to adult mice attenuated disease in models of colitis and allergic diarrhoea. Use of the isolated strains may allow for tailored therapeutic manipulation of human immune disorders.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Eco-Systems Biology (Wilmes Group)
Disciplines :
Microbiology
Author, co-author :
Atarshi, Koji 
Tanoue, Takeshi 
Oshima, Kenshiro 
Suda, Wataru
Nagano, Yuji
Nishikawa, Hiroyoshi
Fukuda, Shinji
Saito, Takuro
Narushima, Seiko
Hase, Koji
Kim, Sangwan
Fritz, Joëlle
WILMES, Paul ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Ueha, Satoshi
Matsushima, Kouji
Ohno, Hiroshi
Olle, Bernat
Sakaguchi, Shimon
Taniguchi, Tadtsugu
Morita, Hidetoshi
Hattori, Masahira
Honda, Kenya
More authors (12 more) Less
 These authors have contributed equally to this work.
External co-authors :
yes
Language :
English
Title :
Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota
Publication date :
08 August 2013
Journal title :
Nature
ISSN :
0028-0836
eISSN :
1476-4687
Publisher :
Nature Publishing Group, Basingstoke, United Kingdom
Volume :
500
Pages :
232-236
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 22 January 2014

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