{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T09:57:30Z","timestamp":1785491850527,"version":"3.56.0"},"reference-count":54,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2022YFF0606700"],"award-info":[{"award-number":["2022YFF0606700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2022YFF0606703"],"award-info":[{"award-number":["2022YFF0606703"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Open Foundation of Shaanxi University of Chinese Medicine Key Laboratory of Research & Development of Characteristic Qin Medicine Resources","award":["KF202330"],"award-info":[{"award-number":["KF202330"]}]},{"award":["KF202330"],"award-info":[{"award-number":["KF202330"]}],"id":[{"id":"https:\/\/ror.org\/021r98132","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Cadmium (Cd), a ubiquitous environmental toxicant, poses substantial health risks even at low-dose chronic exposures. In this study, we developed a mouse model with chronic low-dose dietary Cd exposure (100 nM CdCl2 in drinking water for eight months) to investigate its impacts on cognitive and neuropathological alterations. Behavioral assessments demonstrated that Cd-exposed mice exhibited pronounced deficits in spatial learning, memory retention, and working memory compared with control mice. Histopathological analyses of hippocampus uncovered accelerated Alzheimer\u2019s-like neuropathology, marked by elevated \u03b2-amyloid plaque immunoreactivity and tau hyperphosphorylation. Concurrently, neuroinflammatory responses were markedly upregulated, shown as astrocytes activation and pro-inflammatory Th17 cell signatures in parenchyma. Brain transcriptomic profiling revealed extracerebral prostaglandin signaling following Cd exposure, a finding consistent with elevated prostaglandins detected in the gut. Crucially, these outcomes were gut microbiota-involved: antibiotic-mediated microbiota depletion attenuated dietary Cd-enhanced cognitive impairments, neuroinflammation, and prostaglandin upregulation, underscoring the critical role of intestinal microbes in mediating Cd neurotoxicity. Furthermore, in vitro co-culture experiments demonstrated that Cd potentiated prostaglandin production in intestinal epithelial cells\u2014an effect amplified by gut bacterial stimuli. This observation suggests a mechanism under which peripheral prostaglandins may contribute to central inflammatory cascades. Together, these findings support a gut-brain mechanism underlying dietary Cd-exacerbated neurodegeneration and highlight gut homeostasis and prostaglandin signaling as promising therapeutic targets for mitigating Cd-associated neurodegenerative disorders.<\/jats:p>","DOI":"10.3390\/toxics14080662","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:47:41Z","timestamp":1785145661000},"page":"662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Environmental Cadmium Exposure Exacerbates Alzheimer\u2019s-like Pathology in a Gut Microbiota-Involved Manner"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2486-1852","authenticated-orcid":false,"given":"Bao","family":"Guo","sequence":"first","affiliation":[{"name":"School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junzhuang","family":"Chang","sequence":"additional","affiliation":[{"name":"Shanghai Chn-Alternative Biotechnology Co., Ltd., Shanghai 201403, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aolu","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Chn-Alternative Biotechnology Co., Ltd., Shanghai 201403, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjie","family":"Li","sequence":"additional","affiliation":[{"name":"College of Energy Environment and Safety Engineering, China Jiliang University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianghong","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujun","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7253-7566","authenticated-orcid":false,"given":"Qian","family":"Ba","sequence":"additional","affiliation":[{"name":"School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"},{"name":"Science and Technology Innovation Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1289\/ehp.0901234","article-title":"Cadmium, environmental exposure, and health outcomes","volume":"118","author":"Satarug","year":"2010","journal-title":"Environ. 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