Background: Mucin-degrading bacteria are densely populated in the intestinal epithelium; however, their interaction with intestinal stem cells (ISCs) and their progeny has 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. A total of 32 fecal samples were obtained from healthy volunteers and A. muciniphila was isolated from 11 samples. Mechanism of A. muciniphila was observed in vivo and in vitro, and studied using organoids, histology, metagenomics, and whole genome sequencing.
Results: We found that 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). 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 content supernatant 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. A novel isotype of A. muciniphila strain was isolated from heathy human feces that possessed improved functions for intestinal epithelial regeneration.
Conclusions: These findings suggest that mucin-degrading bacteria (such as A. muciniphila)
may play a crucial role in promoting ISC-mediated epithelial development and contribute to intestinal homeostasis maintenance.