Mucin degrading bacteria accelerates intestinal stem cells-derived epithelial development

Abstract

Abstract Mucin degrading bacteria are closely located in intestinal epithelium; however, how they associate differentiation and development of intestinal stem cells (ISCs) is not elucidated. To address an exact role of mucin degrading bacteria on the gut homeostasis, mice were fed with Akkermansia muciniphila, which is specialized to mucin degradation, for one month. We found that oral feeding with A. muciniphila accelerated self-renewal of Lgr5+ ISCs and promoted differentiation of lysozyme+ Paneth cells and Muc2+ goblet cells in the small intestine. Co-cultured with Lgr5+ ISCs and Paneth cells from A. muciniphila-fed mice resulted in augmented organoid forming capacity in comparison to those from PBS-fed control mice in a Wnt3-dependant manner. Of note, levels of acetate and propionate were higher in cecum contents of A. muciniphila-fed mice than those of control mice. Organoids treated with cecum contents obtained from A. muciniphila-fed mice exhibited larger size and these effects were diminished by Gpr41/43 antagonists. In addition, oral feeding with A. muciniphila induced change of gut microbiota composition and a positive correlation between several genus including Akkermansia. Most importantly, pre-treatment with A. muciniphila prevented intestinal epithelial cells damage caused by radiation and chemotherapy. These findings suggest that mucin degrading bacteria (i.e., A. muciniphila) play a crucial role in promoting ISCs-mediated epithelial development and contributed to maintain intestinal homeostasis.