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How gut bacteria use a bile acid to keep inflammation in check

Using cultured cells, mouse models, and human samples, scientists have discovered how certain bacteria might suppress gastrointestinal inflammation by modifying a bile acid in the gut. The human gastrointestinal tract is teeming with trillions of bacteria that can aid digestion and influence health and disease. To prevent undue inflammation in the gut—like what occurs in inflammatory bowel disease (IBD)—it is important to understand how gut bacteria coexist with the immune system, which must strike a delicate balance between tolerating friendly bacteria and attacking disease-causing microbes. It has been shown previously that 3-oxolithocholic acid (3-oxoLCA), a chemical compound derived from a liver bile acid, may help suppress gut inflammation by preventing T cells (a class of cells involved in immune responses) from developing into inflammation-promoting “T helper” cells. It was unclear exactly how 3-oxoLCA was being produced from bile acids, however, and whether it plays a role in preventing gut inflammation. Knowing these important details could lead to the development of new treatments for IBD.

Using fecal samples from volunteers, a team of scientists was able to identify several species of gut bacteria that can break down the bile acid lithocholic acid (LCA) to generate the compounds that suppress T cell activation. They found that these bacteria—with at least some working in concert—can modify LCA to generate 3-oxoLCA and the abundant bile acid derivative isolithocholic acid (isoLCA), both of which could prevent T cells from transforming into specific types of inflammation-promoting T helper cells. Likewise, male and female mice colonized with these bacteria could convert LCA into 3-oxoLCA and isoLCA, and these mice also had lower levels of inflammation-promoting T helper cells. Importantly, the researchers analyzed samples from men and women and found that people with IBD had lower levels of LCA-converting bacteria— and lower levels of 3-oxoLCA and isoLCA—compared to people without IBD. They also had more markers of inflammation-promoting T helper cells. This suggests that high levels of LCA-derived compounds produced by certain gut bacteria may help prevent IBD by suppressing the gut’s immune response. Altogether, these results offer a deeper understanding of how microbes can control the immune system in the gut to prevent inflammation, and they offer new approaches to develop potential therapies for IBD by promoting immune tolerance.

Paik D, Yao L, Zhang Y, …Devlin AS. Human gut bacteria produce ΤΗ17-modulating bile acid metabolites. Nature 603: 907-912, 2022.

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