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Our preliminary research demonstrated that mice colonized with fecal microbiota from OCD patients developed compulsive\u2010like behaviors, associated with a significant increase in the microbial metabolite succinate. However, the mechanisms linking succinate to compulsive\u2010like behavior remain to be fully elucidated. Here, we demonstrate that succinate is associated with significant compulsive\u2010like behaviors. Succinate is associated with disruptions of glutamatergic neurons within the dorsal medial prefrontal cortex (dmPFC), and we characterize dual pathways linked to the behavioral abnormality: both by dmPFC microglial engagement via the succinate cognate receptor SUCNR1, and by gut\u2010to brain signaling conveyed through vagal afferents and the 5\u2010HT\n                    <jats:sub>4<\/jats:sub>\n                    receptor. Pharmacological modulation of the succinate metabolism pathway through succinate dehydrogenase inhibition ameliorates compulsive\u2010like behavior in\n                    <jats:italic>Hoxb8<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    OCD\u2010model mice. Circulating succinate levels significantly distinguish OCD patients from healthy controls with an AUC of 0.73, and correlate with prefrontal cortex activity on functional imaging. Collectively, our study delineates a gut\u2010brain axis implicating succinate in central nervous system dysregulation associated compulsive\u2010like behavior, elucidates novel immunometabolism and neural circuit mechanisms underlying OCD pathogenesis, and identifies druggable targets for potential precise interventions.\n                  <\/jats:p>","DOI":"10.1002\/advs.77836","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:00:31Z","timestamp":1790532031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Gut\u2010Brain Axis Underlying Succinate\u2010Associated Compulsive\u2010Like Behavior"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8211-3823","authenticated-orcid":false,"given":"Yi","family":"Li","sequence":"first","affiliation":[{"name":"Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Shanghai 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