Diet-driven differential response of Akkermansia muciniphila modulates pathogen susceptibility

Mathis Wolter, Erica T. Grant, Marie Boudaud, Nicholas A. Pudlo, Gabriel V. Pereira, Kathryn A. Eaton, Eric C. Martens, Mahesh S. Desai*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)596-625
Number of pages30
JournalMolecular Systems Biology
Volume20
Issue number6
Early online date14 May 2024
DOIs
Publication statusPublished - Jun 2024

Keywords

  • Akkermansia muciniphila
  • Citrobacter rodentium
  • Community Ecology
  • Dietary Fiber
  • Synthetic Gut Microbiota

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