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Adv."],"published-print":{"date-parts":[[2025,11,28]]},"abstract":"<jats:p>\n                    Intermittent fasting (IF) offers a potential strategy to counteract Alzheimer\u2019s disease (AD) progression. In our 16-week study on AD transgenic mice, IF positively affected cognitive function and reduced amyloid-\u03b2 (A\u03b2) accumulation, verifying the IF\u2019s role in modulating neuroinflammation. Multiomics integration revealed strong links between IF-induced hippocampal gene expression, gut microbiota, and serum metabolites beneficial for cognition. Indole-3-propionic acid (IPA) emerged as a pivotal microbial metabolite. Blocking its neuronal receptor, pregnane X receptor (PXR), abolished IF\u2019s effects. Human data paralleled these findings, showing lower IPA levels in patients with mild cognitive impairment and AD than in controls. IPA supplementation and IPA-producing\n                    <jats:italic toggle=\"yes\">Clostridium sporogenes<\/jats:italic>\n                    reproduced IF\u2019s cognitive benefits, whereas PXR blockade in neurons or disruption of IPA synthesis abrogated them. IPA crossed the blood-brain barrier, exhibited potent anti-inflammatory activity, and suppressed A\u03b2 accumulation, essential for neuroprotection. These results underscore microbial metabolites regulated by IF, particularly IPA, as therapeutic candidates for AD, highlighting the critical role of the gut-brain axis in neurodegeneration.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adw8410","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T18:58:56Z","timestamp":1764356336000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":24,"title":["Gut microbial-derived indole-3-propionate improves cognitive function in Alzheimer\u2019s disease"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1925-091X","authenticated-orcid":true,"given":"Ling","family":"Li","sequence":"first","affiliation":[{"name":"College of Food Science and Engineering, Northwest A&amp;F University, Yangling 712100, 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