Akkermansia muciniphila Selectively Reshapes Small Intestinal Cell Populations

The gastrointestinal tract harbors a dynamic microbial ecosystem that interfaces with the intestinal epithelium. Among this community, Akkermansia muciniphila , a mucin-degrading microbe, has garnered attention for its impact on gut health. While well studied in the colon, its influence on the small intestine remains underexplored. To examine direct effects of A. muciniphila , we used gnotobiotic mice. Germ-free mice were inoculated with Brain Heart Infusion (BHI) media or 10⁹ viable A. muciniphila in BHI. After 21 days, small intestinal tissue was collected. Fluorescence in situ hybridization confirmed A. muciniphila colonization. Immunofluorescence staining revealed increased epithelial cell proliferation, unchanged goblet cell numbers, but altered mucus composition with reduced fucose residues. Tuft cell numbers and group 2 innate lymphoid cells (ILC2s) were also elevated in A. muciniphila -colonized mice. Analysis of conditioned media and the A. muciniphila genome identified succinate production, a metabolite known to expand tuft cells. Thus, A. muciniphila alone is sufficient to increase tuft cells in the small intestine, potentially via succinate signaling. These findings reveal a novel role for A. muciniphila in regulating gastrointestinal homeostasis.