Further butyrate potential
Besides the prospects of harnessing butyrate as a therapeutic for IBD, the results open opportunities in a range of other inflammatory, Treg cell–dependent diseases.
“It would be interesting to see if the findings apply not only to mucosal inflammation in the intestine but also to organ-specific autoimmune diseases such as type 1 diabetes and sterile inflammation,” said Shimon Sakaguchi, a professor of experimental immunology at the
Immunology Frontier Research Center at Osaka University.
Mathis was less sanguine, noting, “There is more and more evidence that Treg cells come in multiple flavors and that inflamed tissues have their own unique populations controlling autoimmunity and inflammatory responses. It is not yet clear to what extent the Treg cells generated in the gut or systemically under these conditions will be able to perform all surveillance and homeostatic functions. Butyrate-induced Treg cell generation might work for some diseases, especially in the intestine, but not others.”
But Sakaguchi added, “Metabolites as well as environmental cues produced by commensal bacteria contain a wide range of immune modulators for innate and adaptive immune cells, so further detailed analyses will be needed to understand integrated immune responses and develop a measure to control the immune balance.”
“Regulatory T cells do play an essential role to avoid excessive inflammatory responses as well as autoimmunity. Therefore, the beneficial effects of butyrate could be applicable for the prevention and possibly also treatment of other autoimmune diseases or allergies—including food allergies—where Treg cells have been implied to be of relevance,” said Daniel. “With respect to inflammatory bowel disease it would be helpful to see specific outcomes in models for Crohn's disease vs. ulcerative colitis—whether butyrate is equally beneficial in both diseases.”
Ohno's team is planning to explore the role of butyrate and of colonic Treg cells in food allergy and to see if they can influence the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis (MS).