ABSTRACTA high-fat (HF) diet reduces resistance to the foodborne pathogen Listeria monocytogenes. We demonstrate that short-term gavage with A. muciniphila increases resistance to oral and systemic L. monocytogenes infection in mice fed a HF diet. A. muciniphila reduced inflammation in the gut and liver of mice fed a high-fat diet prior to infection and reduced inflammatory cell infiltration in the ileum to levels similar to mice fed a low-fat (LF) diet. Akkermansia administration had minimal impacts upon the microbiota and microbial metabolites and did not affect individual taxa or impact the Bacteroidetes to Firmicutes ratio. In summary, A. muciniphila increased resistance to L. monocytogenes infection in mice fed a HF diet by moderating immune/physiological effects through specific interaction between A. muciniphila and the host gut.