Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota

Koji Atarashi, Takeshi Tanoue, Kenshiro Oshima, Wataru Suda, Yuji Nagano, Hiroyoshi Nishikawa, Shinji Fukuda, Takuro Saito, Seiko Narushima, Koji Hase, Sangwan Kim, Joëlle V. Fritz, Paul Wilmes, Satoshi Ueha, Kouji Matsushima, Hiroshi Ohno, Bernat Olle, Shimon Sakaguchi, Tadatsugu Taniguchi, Hidetoshi MoritaMasahira Hattori, Kenya Honda

Research output: Contribution to journalArticle

1245 Citations (Scopus)

Abstract

Manipulation of the gut microbiota holds great promise for the treatment of inflammatory and allergic diseases. Although numerous probiotic microorganisms have been identified, 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 (T reg)-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 T reg -cell-inducing species. From these mice, we isolated and selected 17 strains of bacteria on the basis of their high potency in enhancing T reg cell abundance and inducing important anti-inflammatory molecules - including interleukin-10 (IL-) and inducible T-cell co-stimulator (ICOS) - in T reg 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 T reg 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.

Original languageEnglish
Pages (from-to)232-236
Number of pages5
JournalNature
Volume500
Issue number7461
DOIs
Publication statusPublished - 2013 Jul 11

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    Atarashi, K., Tanoue, T., Oshima, K., Suda, W., Nagano, Y., Nishikawa, H., Fukuda, S., Saito, T., Narushima, S., Hase, K., Kim, S., Fritz, J. V., Wilmes, P., Ueha, S., Matsushima, K., Ohno, H., Olle, B., Sakaguchi, S., Taniguchi, T., ... Honda, K. (2013). Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature, 500(7461), 232-236. https://doi.org/10.1038/nature12331