New Northwestern Medicine research published in Nature Communications suggests that a substance produced when gut bacteria digest dietary fiber may leave a durable molecular mark on cells lining the intestine, promoting immune tolerance and potentially helping protect against inflammatory bowel disease-like conditions even after exposure to the metabolite has ended. The researchers found that beneficial compounds made by gut microbes can effectively “train” the intestinal lining, helping it preserve immune tolerance over time.

One major question remained unresolved: how butyrate in the gut is rapidly absorbed and metabolized by intestinal epithelial cells (IECs), which limits the amount of free butyrate that can directly reach underlying immune cells. The researchers supplied mice with butyrate in their drinking water for a set period, then ended the treatment. Two weeks after the butyrate had been withdrawn, CD4+ T-cells were still producing elevated levels of IL-10, an important anti-inflammatory cytokine that helps control intestinal inflammation.

The treated mice were also more resistant to chemically induced colitis compared with untreated animals, losing less weight, having lower levels of inflammatory markers, and developing less severe tissue damage. This protection depended on IL-10 signaling. The researchers determined that the lasting effect did not result from changes to the gut microbiome itself but rather from IECs secreting immunoregulatory factors after butyrate treatment, which can act on T-cells. They identified N1-acetylspermidine as a likely candidate for carrying this signal, and found that it increased IL-10 production in T-cells and accounted for part of the immune-regulating activity generated by epithelial cells exposed to butyrate.

This is a summary. Read the original at sciencedaily.com.