Bacterial constipation: Mucin-degrading intestinal commensal bacteria cause constipation

Area of Science:

• Gastroenterology
• Microbiology
• Microbiome Research

Background:

• Constipation is a prevalent gastrointestinal disorder with poorly understood microbial contributions.
• Specific gut commensals, Akkermansia muciniphila and Bacteroides thetaiotaomicron, are implicated in constipation pathogenesis.

Purpose of the Study:

• To elucidate the mechanistic role of A. muciniphila and B. thetaiotaomicron in constipation.
• To investigate the cooperative interaction between these bacteria in inducing constipation.
• To identify potential therapeutic targets for bacterial constipation.

Main Methods:

• Comparative analysis of gut microbiota in constipated patients (Parkinson's disease and chronic idiopathic constipation) and healthy controls.
• Gnotobiotic mouse models colonized with single or combined bacterial strains.
• Generation of an anaerobic sulfatase-maturating enzyme (anSME)-deficient B. thetaiotaomicron mutant.
• Analysis of fecal mucin composition and gene expression.

Main Results:

• A. muciniphila and B. thetaiotaomicron were found in increased abundance in constipated patients.
• Co-colonization of gnotobiotic mice with both bacteria induced constipation, while single colonization did not.
• An anSME-deficient B. thetaiotaomicron strain ameliorated constipation in co-colonized mice, indicating the role of mucin sulfate catabolism.
• Bacterial degradation of fecal mucins reduces lubrication and leads to fecal dehydration.

Conclusions:

• A. muciniphila and B. thetaiotaomicron cooperatively induce constipation through mucin degradation.
• Bacterial constipation involves the synergistic action of sulfatase and glycosylase activities on colonic mucins.
• Targeting microbial sulfatase activity presents a promising therapeutic strategy for bacterial constipation.