In February, I entitled a post “Bile Acids, Inflammatory Bowel Disease, and the Microbiome: A Rapidly Developing Story.” Well, that rapidly developing story has taken another leap forward. A new paper was just published in the journal, Nature, that shows that a metabolite produced by gut bacteria, called isoDCA, boosts levels of regulatory T regulatory cells (Tregs) in the intestines.[i] (You’ll all remember that the regulatory part of the immune system modulates our inflammatory response so that we can keep it in check. In humans and our domesticated animals living in the industrialized world, the regulatory system tends to be too low to keep us from experiencing excessive inflammation…and thus, the epidemic of autoimmune, allergic and other inflammatory disorders.) By suppressing excessive inflammation in the colon, this molecule may lower the risk for colon cancer.
Remember that bile acids, which we use to digest fat, are converted into secondary bile acids by gut bacteria and these secondary bile acids are themselves immune signaling molecules: “Although most bile acids are transported back into the liver via enterohepatic circulation, a small fraction of this pool (roughly 5%) escapes reabsorption in the ileum and is subject to further bacterial transformation in the colon, giving rise to secondary bile acids.”
These scientists looked at how these metabolized bile acids influence the local immune system of the intestines, including how they affect the production of Tregs and dendritic cells, “…which help direct the generation of Tregs”[ii] They discovered that two secondary bile acid molecules (ω-MCA and isoDCA) boost the conversation of precursors of Tregs into Tregs themselves. Since isoDCA is more abundant in humans, they focused in on it and discovered that it actually works by influencing how dendritic cells work: instead of expressing genes that lead to a pro-inflammatory response, isoDCA directs them into an anti-inflammatory state in which they drive a greater production of Tregs.
They proceeded to test this in vivo, in mice, giving the animals a variety of bacteria (Bacteroides) engineered to make isoDCA and discovered that indeed, this led to greater numbers of Tregs in their intestines.
Says the lead researcher: “People have been thinking about using commensal microbes to treat inflammatory disorders of the colon…One approach is to develop a new class of drugs made from defined consortia of microbes that would limit inflammation and promote colonic health, reducing the risk of colon cancer in people. Bacterial consortia that produce isoDCA and other metabolites that promote anti-inflammatory activity in colon-resident immune cells could be one of the components of such interventions.”
According to the CDC, colorectal cancer is the third most common cancer as well as the third leading cause of cancer related deaths in the United States[iii]. A new means of reducing the rate of this cancer via a probiotic sounds like a pretty darn great idea to me.
[i] Clarissa Campbell et al, Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells, Nature (2020). DOI: 10.1038/s41586-020-2193-0