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Given increasing real\u2010world co\u2010exposure to lead (Pb) and cadmium (Cd), elucidating RSV's capacity to preserve gut\u2013brain axis (GBA) homeostasis has direct translational relevance for populations relying on phytochemical interventions. Sprague\u2013Dawley rats were randomized into control, Pb\u2013Cd model, and RSV treatment groups (10, 20, or 40\u2009mg\/kg). For 4\u2009weeks, rats received Pb (300\u2009mg\/L) and Cd (50\u2009mg\/L) in drinking water with daily RSV. Cognitive function was assessed by Morris water maze; barrier integrity by Evans blue assay, histology, and Western blot for ZO\u20101\/Occludin; synaptic ultrastructure by TEM; microbiota composition by 16S rRNA sequencing; and short\u2010chain fatty acids (SCFAs) by GC\u2010MS. Neurotransmitters (5\u2010HT, GABA, SP, VIP) and cytokines (IL\u20106, IL\u20101\u03b2, TNF\u2010\u03b1) were measured by ELISA. RSV improved spatial learning, reduced EB extravasation, preserved synaptic ultrastructure and proteins (BDNF, SYN, PSD\u201095), and restored intestinal architecture with increased ZO\u20101\/Occludin. RSV attenuated cytokine release, normalized goblet cells, reversed dysbiosis by restoring Lactobacillaceae\/Prevotellaceae, and increased acetate, propionate, and butyrate. It reinstated 5\u2010HT and GABA while reducing SP and restoring VIP across serum, colon, and hippocampus. RSV attenuated Pb\u2013Cd\u2013associated neurotoxicity and was accompanied by improved intestinal and BBB\u2010related readouts, partial normalization of gut microbiota features and SCFA levels, and preservation of synaptic and neurotransmitter\u2010related markers, consistent with a link to gut\u2013brain axis function. This study is among the first to test RSV in a Pb\u2013Cd co\u2010exposure model using a multi\u2010dose regimen with integrated behavioral, barrier, microbial, and neurochemical endpoints.<\/jats:p>","DOI":"10.1002\/ptr.70301","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:04:18Z","timestamp":1773705858000},"page":"3047-3062","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Resveratrol Attenuates Neuroinflammation and Gut\u2013Brain Axis Dysfunction Induced by Lead and Cadmium Co\u2010Exposure by Modulating Gut Microbiota in Rats"],"prefix":"10.1002","volume":"40","author":[{"given":"Huimao","family":"Liu","sequence":"first","affiliation":[{"name":"Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Yang","sequence":"additional","affiliation":[{"name":"Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Cao","sequence":"additional","affiliation":[{"name":"Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Song","sequence":"additional","affiliation":[{"name":"Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3116-1478","authenticated-orcid":false,"given":"Yuanfeng","family":"Zou","sequence":"additional","affiliation":[{"name":"Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Li","sequence":"additional","affiliation":[{"name":"Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renyong","family":"Jia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyue","family":"Li","sequence":"additional","affiliation":[{"name":"Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1752-644X","authenticated-orcid":false,"given":"Zhongqiong","family":"Yin","sequence":"additional","affiliation":[{"name":"Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Agency for Toxic Substances and Disease Registry (ATSDR).2012.\u201cToxicological Profile for Cadmium.\u201dU.S. Department of Health and Human Services Public Health Service. 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