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Here, we purified a pectin polysaccharide (GP) from guava fruits (Mw 94.516 kDa), featuring a backbone of HG and RG-I domains with side chains of \u21923,6)-\u03b2-d-Galp-(1\u2192 and \u21925)-\u03b1-l-Araf -(1\u2192, and evaluated its neuroprotective effects in a dNCR mouse model. Our results demonstrated that GP ameliorates cognitive impairment, pathological damage, neuroinflammation, and oxidative stress injury, while inhibiting the pGSK-3\u03b2\/pTau signaling pathway and A\u03b2 deposition. Findings further reveal that GP ameliorates gut microbiota (GM) dysbiosis, enhances the production of short-chain fatty acids (SCFAs), and suppresses the key enzymes and metabolites in the AA metabolic pathway in dNCR mice. However, antibiotic treatment abolished the effects of GP, indicating that GP modulates the GM\u2013AA metabolism axis to suppress A\u03b2\/Tau pathology, thereby mitigating the progression of dNCR.<\/jats:p>","DOI":"10.1021\/acs.jafc.5c17336","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:02:41Z","timestamp":1787238161000},"page":"27075-27095","source":"Crossref","is-referenced-by-count":0,"title":["Guava Polysaccharide\nInterventions Ameliorate Delayed\nNeurocognitive Recovery by Modulating the Gut Microbiota\u2013Arachidonic\nAcid Metabolism Axis and Attenuating A\u03b2\/Tau Pathology"],"prefix":"10.1021","volume":"74","author":[{"given":"Qin","family":"Gao","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital of Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330006"]},{"name":"Key Laboratory of Anesthesiology of Jiangxi Province , , ,","place":["Nanchang, Jiangxi, China, 330006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Chen","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330006"]},{"name":"Key Laboratory of Anesthesiology of Jiangxi Province , , ,","place":["Nanchang, Jiangxi, China, 330006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Yu","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Zeng","sequence":"additional","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Nan","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330006"]},{"name":"Key Laboratory of Anesthesiology of Jiangxi Province , , ,","place":["Nanchang, Jiangxi, China, 330006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deju","family":"Zhang","sequence":"additional","affiliation":[{"name":"The University of Hong Kong , , Pokfulam Road , ,","place":["Hong Kong, China, 999077"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University , , Yanjiang Road , ,","place":["Guangzhou, China, 510120"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Xiao","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Huang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Deng","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Xiong","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehong","family":"Zheng","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuxiang","family":"Cai","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6387-1759","authenticated-orcid":true,"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330006"]},{"name":"Key Laboratory of Anesthesiology of Jiangxi Province , , ,","place":["Nanchang, Jiangxi, China, 330006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuchun","family":"Yu","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330006"]},{"name":"Key Laboratory of Anesthesiology of Jiangxi Province , , 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