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Short-Chain Fatty Acids Produced by Ruminococcaceae Mediate α-Linolenic Acid Promote Intestinal Stem Cells Proliferation
Authors:Jing Xie  Ling-fei Li  Tian-yi Dai  Xin Qi  Yan Wang  Tiao-zhen Zheng  Xiao-yu Gao  Yun-juan Zhang  Yu Ai  Li Ma  Song-lin Chang  Feng-xian Luo  Yang Tian  Jun Sheng
Abstract: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, it is found that ALA (0.5 g kg?1) promotes small intestinal and villus growth by activating the Wnt/β-catenin signaling pathway to stimulate the proliferation of ISCs. Furthermore, ALA administration increases the abundance of the Ruminococcaceae and Prevotellaceae, and promotes the production of short-chain fatty acids (SCFAs). Subsequent fecal transplantation and antibiotic experiments demonstrate that ALA on the proliferation of ISCs are gut microbiota dependent, among them, the functional microorganism may be derived from Ruminococcaceae. Administration of isobutyrate shows a similar effect to ALA in terms of promoting ISCs proliferation. Furthermore, ALA mitigates 5-fluorouracil-induced intestinal mucosal damage by promoting ISCs proliferation. Conclusion : These results indicate that SCFAs produced by Ruminococcaceae mediate ALA promote ISCs proliferation by activating the Wnt/β-catenin signaling pathway, and suggest the possibility of ALA as a prebiotic agent for the prevention and treatment of intestinal mucositis.
Keywords:gut microbiota  intestinal stem cells  short-chain fatty acids  the Wnt/β  -catenin signaling pathway  α  -linolenic acid
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