The Impact of Akkermansia muciniphila on Mouse Models of Depression, Anxiety, and Stress: A Systematic Review and Meta-Analysis

Background: Akkermansia muciniphila (A. muciniphila), a bacterial species within the human gut microbiome, has shown beneficial effects on host health. Emerging research suggests that A. muciniphila also influences neurobehavioral domains through the microbiota-gut-brain axis. This meta-analysis evaluates A. muciniphila’s impact on depression, anxiety, and stress in mouse models. Methods: We conducted a systematic search of PubMed, Science Direct, Embase, and Web of Science databases up to March 2024, identifying 15 eligible studies. Results: Supplementation with A. muciniphila, its outer membrane protein (Amuc_1100), and extracellular vesicles (EVs) alleviated anxiety, depressive-like behaviors, and enhanced memory in mice. Compared to controls, intervention groups exhibited reduced anxiety-like behaviors, including increased travel distance in the open-field test (OFT) and more time spent in the lightbox during the light-dark box (LDB) test and open arms in the elevated plus maze (EPM). Depression-like symptoms were reduced, with lower immobility time in the tail suspension and forced swim tests. Memory function also improved, and learning time was reduced in the Y-maze and Barnes circular maze tests. Serotonin levels increased significantly in the serum and hippocampus, while corticosterone levels decreased, though not significantly. The intervention reduced hippocampal and serum inflammatory markers (TNFα, IL1β, IL6) and altered gut microbiome composition, increasing Akkermansia, Roseburia, Caldicoprobacter, and Lachnospiraceae. Conclusion: This meta-analysis provides evidence supporting the health-promoting effects of A. muciniphila, one of the next-generation probiotics, in alleviating neuropsychiatric disorders. Given the high prevalence and clinical significance of depression, anxiety, and stress, further investigation into the therapeutic utility of A. muciniphila is warranted.