Short-chain fatty acids produced by Ruminococcaceae mediates α-Linolenic acid promote intestinal stem cells proliferation.

SCOPE The proliferation and differentiation of intestinal stem cells (ISCs) are the basis of intestinal renewal and regeneration, and gut microbiota plays an important role in it. Dietary nutrition has the effect of regulating the activity of ISCs, however, the regulation effect of α-linolenic acid (ALA) has seldom been reported. METHODS AND RESULTS After intervening mice with different doses of ALA for 30 days, we found that ALA (0.5 g/kg) promoted small intestinal and villus growth by activating the Wnt/β-catenin signaling pathway to stimulate the proliferation of ISCs. Furthermore, ALA administration increased the abundance of the Ruminococcaceae and Prevotellaceae, and promoted the produce of short-chain fatty acids (SCFAs). Subsequent fecal transplantation and antibiotic experiments demonstrated that ALA on the proliferation of ISCs are gut microbiota dependent, among them the functional microorganism may be derived from Ruminococcaceae. Administration of isobutyrate showed a similar effect to ALA in terms of promoting ISCs proliferation. Furthermore, ALA mitigated 5-fluorouracil-induced intestinal mucosal damage by promoting ISCs proliferation. CONCLUSION These results indicate that SCFAs produced by Ruminococcaceae mediates ALA promote ISCs proliferation by activating Wnt/β-catenin signaling pathway, and suggest the possibility of ALA as a prebiotic agent for the prevention and treatment of intestinal mucositis. This article is protected by copyright. All rights reserved.