<i>Akkermansia muciniphila</i> Selectively Reshapes Small Intestinal Cell Populations

The gastrointestinal tract harbors a dynamic microbial ecosystem that interfaces with the intestinal epithelium. Among this community, <i>Akkermansia muciniphila</i>, 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 <i>A. muciniphila</i>, we used gnotobiotic mice. Germ-free mice were inoculated with Brain Heart Infusion (BHI) media or 10⁹ viable <i>A. muciniphila</i> in BHI. After 21 days, small intestinal tissue was collected. Fluorescence in situ hybridization confirmed <i>A. muciniphila</i> 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 <i>A. muciniphila</i>-colonized mice. Analysis of conditioned media and the <i>A. muciniphila</i> genome identified succinate production, a metabolite known to expand tuft cells. Thus, <i>A. muciniphila</i> alone is sufficient to increase tuft cells in the small intestine, potentially via succinate signaling. These findings reveal a novel role for <i>A. muciniphila</i> in regulating gastrointestinal homeostasis.