The distal colon is rich in anaerobes whose production of short-chain fatty acids (SCFAs) from dietary fiber has been linked to the control of inflammatory bowel disease. In Cell Host & Microbe, Colgan and colleagues demonstrate how SCFAs, in particular butryate, can regulate gut homeostasis. The addition of butyrate to colonic epithelial cells increases mitochondria-dependent oxygen consumption and contributes to the hypoxic environment of the colonic lumen. Diminished cellular oxygen leads to the stabilization of HIF, a chief transcriptional regulator of inflammation and the response to lower oxygen tension. Accordingly, the addition of butyrate results in the expression of HIF-regulated genes and, most pertinently, those encoding products involved in maintaining epithelial barrier function. These findings demonstrate not only how SCFAs lead to a clement environment for colonic anaerobes but also how SCFAs can maintain epithelial barrier integrity and thereby influence the development of inflammatory bowel disease.

Cell Host Microbe 17, 662–671 (2015)