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Cadmium (Cd) is a widespread environmental neurotoxicant that disrupts the gut-brain axis and impairs hippocampus-dependent learning and memory, yet effective preventive interventions are lacking. In this study, we discovered that oral supplementation with human fecal microbiome-derived\n                  <jats:italic>A. muciniphila<\/jats:italic>\n                  prevented Cd-induced cognitive impairment in mice throughout 9 weeks of oral Cd exposure at a human body burden-relevant concentration. Notably, brain Cd concentrations were not affected by\n                  <jats:italic>A. muciniphila<\/jats:italic>\n                  supplementation, indicating that cognitive protection was mediated through gut-brain signaling rather than affecting metal accumulation in the brain. Multi-omics characterization identified coordinated gut-brain pathways underlying this protective effect.\n                  <jats:italic>A. muciniphila<\/jats:italic>\n                  preserved Cd-suppressed\n                  <jats:italic>Lactobacillus<\/jats:italic>\n                  taxa (\n                  <jats:italic>L. crispatus, L. intestinalis, L. taiwanensis<\/jats:italic>\n                  ), which positively correlated with cognitive performance, and restored intestinal tight-junction integrity across multiple intestinal sections, particularly the ileum.\n                  <jats:italic>A. muciniphila<\/jats:italic>\n                  also normalized Cd-induced cytokine dysregulation in the serum. In addition, colonic branched-chain fatty acids (BCFAs) emerged as candidate gut-brain mediators, with 2-methylpentanoic acid showing a robust negative correlation with cognitive performance. These\n                  <jats:italic>A. muciniphila<\/jats:italic>\n                  -mediated changes across gut microbiome, intestinal barrier, systemic cytokines, and microbial metabolites coincided with reversal of Cd-induced hippocampal transcriptional alterations regulating synaptic and vascular signaling. Together, this study identified\n                  <jats:italic>A. muciniphila<\/jats:italic>\n                  as a preventive microbiome-based strategy against environmental Cd neurotoxicity in mice, demonstrated that the gut microbial homeostasis can confer cognitive resilience independently of brain toxicant burden, and revealed distinct BCFAs as potential gut-brain mediators of heavy-metal-induced cognitive decline.\n                <\/jats:p>","DOI":"10.64898\/2026.07.31.740339","type":"posted-content","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T04:55:13Z","timestamp":1785992113000},"source":"Crossref","is-referenced-by-count":1,"title":["<i>Akkermansia muciniphila<\/i>\n                  prevents cadmium-induced cognitive impairment through gut microbiome\u2013mediated mechanisms"],"prefix":"10.64898","author":[{"given":"Hao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI. 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