Diet-driven differential response of Akkermansia muciniphila modulates pathogen susceptibility

Mol Syst Biol. 2024 Jun;20(6):596-625. doi: 10.1038/s44320-024-00036-7. Epub 2024 May 14.

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.

Keywords: Akkermansia muciniphila; Citrobacter rodentium; Community Ecology; Dietary Fiber; Synthetic Gut Microbiota.

MeSH terms

  • Akkermansia*
  • Animals
  • Citrobacter rodentium* / pathogenicity
  • Colon / microbiology
  • Diet
  • Dietary Fiber / metabolism
  • Disease Susceptibility
  • Enterobacteriaceae Infections / microbiology
  • Gastrointestinal Microbiome*
  • Germ-Free Life
  • Humans
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Verrucomicrobia / genetics

Substances

  • Dietary Fiber

Supplementary concepts

  • Akkermansia muciniphila