Editors' ChoiceMicrobiome

Pitfalls of probiotics

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Science Translational Medicine  07 Dec 2016:
Vol. 8, Issue 368, pp. 368ec194
DOI: 10.1126/scitranslmed.aal2803

Interleukin-17 (IL-17)–producing T helper 17 (TH17) cells are important to prevent bacterial and fungal infection. Conversely, animal models and clinical trials of IL-17–blocking antibodies in humans have established a pathogenic role for TH17 cells in autoimmune diseases, such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). In mice, intestinal TH17 cell abundance can be modulated using segmented filamentous bacteria (SFB), suggesting a treatment strategy for both infection and autoimmune disease. However, SFB do not persistently colonize the human intestine, and bacteria from humans with comparable properties are unknown. Now, Tan et al. have pushed the field beyond this knowledge gap.

The group found that three of 39 human gut bacterial species flushed into the stomach of mice were able to robustly induce TH17 cells in the small intestine. Mice given the most potent bacterium, B. adolescentis, had no histological evidence of inflammation or tissue destruction, and the expanded TH17 cells did not have a highly pathogenic gene expression signature. In contrast, in a transgenic mouse model of RA, B. adolescentis exacerbated joint thickening in association with more small intestinal TH17 cells and elevated titers of autoantibodies. Humans with IBD were found to have elevated gut levels of B. adolescentis, adding to the uncertainty as to whether these bacteria are harmful or helpful. One lead as to how B. adolescentis can be both symbiotic in health and counterproductive in disease comes from the finding that it also modestly expanded a subset of regulatory T (Treg) cells in mice, which may limit local gut inflammation.

Four of six probiotic formulations containing Bifidobacterium species (but not B. adolescentis) induced TH17 cells in mice, but the ability of these formulations to exacerbate autoimmune disease was not tested. Probiotic supplements are marketed and sold directly to consumers and are generally considered safe. Is it possible that patients with inflammatory diseases are ingesting harmful bacteria? The answer depends on testing the capacity of other bacteria in available probiotics to induce TH17 and Treg cells, determining whether these bacteria drive expansion of TH17 cells and progression of inflammatory disease in humans and understanding how these species interact with the rest of the gut microbiota.

T. G. Tan et al., Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice. Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1617460113 (2016). [Abstract]

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