Diet-driven Differential Response of Akkermansia Muciniphila Modulates Pathogen Susceptibility

Overview

Journal Mol Syst Biol

Specialty Molecular Biology

Date 2024 May 14

PMID 38745106

Authors

Mathis Wolter

Erica T Grant

Marie Boudaud

Nicholas A Pudlo

Gabriel V Pereira

Kathryn A Eaton

Eric C Martens

Mahesh S Desai

Affiliations

Soon will be listed here.

Abstract

The erosion of the colonic mucus layer by a dietary fiber-deprived gut microbiota results in heightened susceptibility to an attaching and effacing pathogen, Citrobacter rodentium. Nevertheless, the questions of whether and how specific mucolytic bacteria aid in the increased pathogen susceptibility remain unexplored. Here, we leverage a functionally characterized, 14-member synthetic human microbiota in gnotobiotic mice to deduce which bacteria and functions are responsible for the pathogen susceptibility. Using strain dropouts of mucolytic bacteria from the community, we show that Akkermansia muciniphila renders the host more vulnerable to the mucosal pathogen during fiber deprivation. However, the presence of A. muciniphila reduces pathogen load on a fiber-sufficient diet, highlighting the context-dependent beneficial effects of this mucin specialist. The enhanced pathogen susceptibility is not owing to altered host immune or pathogen responses, but is driven by a combination of increased mucus penetrability and altered activities of A. muciniphila and other community members. Our study provides novel insights into the mechanisms of how discrete functional responses of the same mucolytic bacterium either resist or enhance enteric pathogen susceptibility.

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