Mucin degrader <i>Akkermansia muciniphila</i> accelerates intestinal stem cell-mediated epithelial development

Abstract

Mucin-degrading bacteria are densely populated in the intestinal epithelium; however, their interaction with intestinal stem cells (ISCs) and their progeny have not been elucidated. To determine whether mucin-degrading bacteria play a role in gut homeostasis, mice were treated with <i>Akkermansia muciniphila</i>, a specialized species that degrades mucin. Administration of <i>A. muciniphila</i> for 4 weeks accelerated the proliferation of Lgr5⁺ ISCs and promoted the differentiation of Paneth cells and goblet cells in the small intestine (SI). We found similar effects of <i>A. muciniphila</i> in the colon. The levels of acetic and propionic acids were higher in the cecal contents of <i>A. muciniphila</i>-treated mice than in PBS-treated mice. SI organoids treated with cecal contents obtained from <i>A. muciniphila</i>-treated mice were larger and could be diminished by treatment with G protein-coupled receptor (Gpr) 41/43 antagonists. Pre-treatment of mice with <i>A. muciniphila</i> reduced gut damage caused by radiation and methotrexate. Further, a novel isotype of the <i>A. muciniphila</i> strain was isolated from heathy human feces that showed enhanced function in intestinal epithelial regeneration. These findings suggest that mucin-degrading bacteria (e.g., <i>A. muciniphila</i>) may play a crucial role in promoting ISC-mediated epithelial development and contribute to intestinal homeostasis maintenance.