Mucin degrader Akkermansia muciniphila 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 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.

Hyaluronan-induced alterations of the gut microbiome protects mice against Citrobacter rodentium infection and intestinal inflammation

“…This idea is strongly supported by our results of A. muciniphila intervention experiments, showing an enhanced resistance to Citrobacter infection and intestinal inflammation in mice inoculated with A. muciniphila. A. muciniphila , a gram-negative and strictly anaerobic bacterium, is the only cultivated intestinal representative of the phylum Verrucomicrobia 28 and has been implicated in gut barrier function, immune response, and host metabolism 29 , 30 . Notably, it has been suggested that reduced levels of A. muciniphila have been observed in patients with obesity, 31 diabetes, 32 metabolic disorders, 33 and inflammatory bowel diseases (mainly ulcerative colitis), 34 which suggests it may have potential role to play in regulating host functions, anti-inflammatory properties and protection against enteropathogenic bacteria infection.…”

Utilization Efficiency of Human Milk Oligosaccharides by Human-Associated Akkermansia Is Strain Dependent

“… Akkermansia muciniphila is a mucin-degrading specialist that colonizes the mucus layer of the human gastrointestinal tract ( 1 ). Paradoxically, Akkermansia also promotes mucus production by enhancing the differentiation of gut epithelial cells, thereby influencing mucosal homeostasis ( 2 ). Numerous positive associations have been observed between this bacterial lineage and human health.…”

Low-Intensity Exercise Modulates Gut Microbiota to Fight Against Radiation-Induced Gut Toxicity in Mouse Models

“…Lactobacillus as well-known probiotics have been proved to be associated with improvement in patients suffering from radiation syndrome in clinical trials ( Linn et al, 2019 ). A recent study has reported that A. muciniphila improves intestinal radiation injury following whole body irradiation ( Kim et al, 2021 ). Notably, the experimental mice in the present study were exposed to abdominal local irradiation, which is more similar to iatrogenic irradiation such as radiotherapy for pelvic and abdominal tumors.…”