A study led by Ludwig MSK Director Alexander Rudensky and published in Nature reported in April that isoDCA, a metabolite of bile acids made by friendly, commensal bacteria in the intestines, boosts the local generation of regulatory T cells—immune cells that suppress autoimmune reactions and inflammation. Such locally generated, or “peripheral”, regulatory T cells (Tregs) help dampen chronic intestinal inflammation, a major driver of colorectal cancers. Alexander and his team screened a spectrum of bile acids produced by bacterial metabolism for such effects in co-cultures of Treg precursors and dendritic cells which, among other things, help direct the generation of Tregs. They showed that isoDCA, which is relatively abundant in the human intestine, opposes the signals issued by a bile acid sensor in dendritic cells, the farnesoid X receptor (FXR). This pushes dendritic cells into an anti-inflammatory state in which they drive the generation of peripheral Tregs. Alexander and his team also showed that mice colonized with bacteria engineered to make isoDCA had many more peripheral Tregs in their intestines than those colonized with the same bacteria tweaked to lack this capability. The discovery has implications for efforts to prevent colon cancer through dietary intervention.
This article appeared in the August 2020 issue of Ludwig Link. Click here to download a PDF (2 MB).