Gut Bacteria May 'Train' the Intestine to Keep Fighting Inflammation, Study Finds

A substance produced when gut bacteria digest dietary fiber may leave a durable molecular mark on the cells lining the intestine, helping protect against inflammatory bowel disease-like conditions even after exposure to the substance has ended, according to new Northwestern Medicine research published in Nature Communications.

The researchers studied butyrate, a short-chain fatty acid (SCFA) that gut bacteria produce by fermenting dietary fiber and that is known to have anti-inflammatory effects. In mice given butyrate in their drinking water and then taken off it, CD4+ T-cells were still producing elevated levels of the anti-inflammatory molecule IL-10 two weeks later. These mice were also more resistant to chemically induced colitis, losing less weight and developing less severe tissue damage than untreated animals; the protection depended on IL-10 signalling. The lasting effect did not depend on changes to the gut microbiome itself — it also appeared in germ-free mice that lack all microbes.

The team traced the effect to intestinal epithelial cells (IECs), which form the physical boundary between the body and the microbiome. In lab experiments, IECs exposed to butyrate caused a strong increase in IL-10 production in both mouse and human T-cells. Using metabolomic analysis, the researchers identified a candidate molecule, N1-acetylspermidine, that increased IL-10 production and accounted for part of this activity. Mechanistically, butyrate acts on IECs to sustain activation of an enzyme called Sat1, which promotes production of N1-acetylspermidine.

"The intestinal epithelium is often viewed as a short-lived barrier reacting to gut contents. Our findings suggest it can also retain a lasting imprint of a microbial metabolite signal," said Tianming Yu, PhD, research assistant professor in the Division of Gastroenterology and Hepatology and the study's first and co-corresponding author. Yingzi Cong, PhD, the Stanley Gradowski Professor of Gastroenterology, was senior and co-corresponding author; N1-acetylspermidine alone did not account for all of the immune-regulating activity observed.