Mucin degrader Akkermansia muciniphila accelerates intestinal stem cell-mediated epithelial development

Gut Microbes. Jan-Dec 2021;13(1):1-20. doi: 10.1080/19490976.2021.1892441.

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 Akkermansia muciniphila, a specialized species that degrades mucin. Administration of A. muciniphila 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 A. muciniphila in the colon. The levels of acetic and propionic acids were higher in the cecal contents of A. muciniphila-treated mice than in PBS-treated mice. SI organoids treated with cecal contents obtained from A. muciniphila-treated mice were larger and could be diminished by treatment with G protein-coupled receptor (Gpr) 41/43 antagonists. Pre-treatment of mice with A. muciniphila reduced gut damage caused by radiation and methotrexate. Further, a novel isotype of the A. muciniphila strain was isolated from heathy human feces that showed enhanced function in intestinal epithelial regeneration. These findings suggest that mucin-degrading bacteria (e.g., A. muciniphila) may play a crucial role in promoting ISC-mediated epithelial development and contribute to intestinal homeostasis maintenance.

Keywords: Gut microbiota; akkermansia muciniphila; epithelial development; g protein-coupled receptors; intestinal stem cells; lgr5; mucin-degrading bacteria; organoids; small intestine.

Publication types

  • Research Support, Non-U.S. Gov't

Grant support

This work was supported by the National Research Foundation of Korea (NRF-2019M3C9A6082487 and NRF-2020R1A2B5B03001450).