During a critical window of early life, colonization of the gut microbiota confers long-lasting beneficial effects on immunity and health outcomes. However, the mechanisms underlying these effects are not clear.
Fang Yan, MD, PhD, and colleagues have identified a probiotic functional factor called p40. Reporting in the journal Cellular and Molecular Gastroenterology and Hepatology, they discovered that p40 enhanced the production of transforming growth factor beta (TGF-beta) through epigenetic modification in intestinal epithelial cells.
In mice in early life, p40 supplementation induced a sustained increase in TGF-beta production, which promoted differentiation of regulatory T cells and protected the gut against inflammation in adulthood. Administering antibodies that neutralized TGF-beta diminished these long-lasting effects.
The researchers concluded that exposure to p40 in early life prevents intestinal inflammation in adulthood through long-lasting epigenetic imprint on TGF-beta in intestinal epithelial cells.
These findings provide a mechanistic rationale for early p40 intervention in individuals at high risk of developing inflammatory bowel disease and other forms of intestinal inflammation.
This research was supported by the National Institutes of Health (grants DK081134, DK056008, DK054993, DK058587, CA077955, CA116087), Crohn’s and Colitis Foundation, and VUMC Digestive Disease Research Center.