Diet-driven differential response of Akkermansia muciniphila modulates pathogen susceptibility.

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. Synopsis: Susceptibility to a mucosal pathogen is both microbiome- and diet-dependent, with mucin specialist Akkermansia muciniphila increasing susceptibility on a fiber-free diet, whereas a fiber-rich diet allows the same commensal to confer resistance. Variations of a 14-member synthetic human gut microbiota show the key role of dietary fiber in determining the severity of Citrobacter rodentium infection through specific members of the microbiome. Combined action of increased mucus barrier permeability and altered community networks underlie the increased pathogen susceptibility in the Akkermansia muciniphila-containing communities fed a fiber-free diet. Exclusion of Akkermansia muciniphila from the synthetic microbiota or consumption of a fiber-rich diet is sufficient to prevent severe infection. Dietary context is key, with the presence of Akkermansia muciniphila protecting against severe infection under fiber-rich conditions. Susceptibility to a mucosal pathogen is both microbiome- and diet-dependent, with mucin specialist Akkermansia muciniphila increasing susceptibility on a fiber-free diet, whereas a fiber-rich diet allows the same commensal to confer resistance. [ABSTRACT FROM AUTHOR]