Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota
- PMID: 23842501
- DOI: 10.1038/nature12331
Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota
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 (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.
Comment in
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Gut microbiota: Selecting Clostridia strains that induce TREG cells from gut microbiota.Nat Rev Gastroenterol Hepatol. 2013 Sep;10(9):504. doi: 10.1038/nrgastro.2013.139. Epub 2013 Jul 23. Nat Rev Gastroenterol Hepatol. 2013. PMID: 23877531 No abstract available.
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Commensal cocktail suppresses gut inflammation.Nat Biotechnol. 2013 Sep;31(9):813. doi: 10.1038/nbt.2680. Nat Biotechnol. 2013. PMID: 24022160 No abstract available.
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