{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:06:00Z","timestamp":1792026360498,"version":"4.4.0"},"reference-count":0,"publisher":"Association of Basic Medical Sciences of FBIH","issue":"2","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomol Biomed"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is increasingly recognised as a disorder that extends beyond the brain, with accumulating evidence implicating gut microbiota\u2013derived metabolites in its onset and progression. This narrative review synthesises 92 peer-reviewed animal, human and meta-analytic studies published between 2010 and 2025 that investigated short-chain fatty acids (SCFAs), tryptophan-derived indoles and kynurenines, trimethylamine N-oxide (TMAO) and secondary bile acids in the context of AD. Collectively, the literature shows that SCFAs support blood\u2013brain-barrier integrity, dampen microglial reactivity and enhance synaptic plasticity, yet can paradoxically amplify \u03b2-amyloid (A\u03b2) deposition under germ-free or supraphysiological conditions, highlighting the importance of host status and dosing. Beneficial indole metabolites such as indole-3-propionic acid counter oxidative stress, strengthen intestinal and cerebral barriers and suppress pro-inflammatory cascades, whereas a shift toward neurotoxic kynurenines correlates with cognitive decline. TMAO emerges as a consistently deleterious metabolite that aggravates endothelial dysfunction, neuroinflammation and A\u03b2 aggregation; dietary precursor restriction and microbial enzyme inhibitors are therefore being explored as mitigation strategies. Secondary bile acids and polyphenol derivatives further modulate mitochondrial bioenergetics and NF-\u03baB signalling, broadening the therapeutic landscape. Multi-omics profiling reveals that AD patients typically exhibit reduced SCFAs and indoles but elevated TMAO, changes that scale with Mini-Mental State Examination scores, brain atrophy and cerebrospinal A\u03b2\u2084\u2082 levels. Early probiotic and faecal-microbiota-transplant trials have begun to normalise these metabolite profiles and yield modest cognitive benefits, underscoring translational potential. Altogether, gut-derived metabolites are not passive by-products but active modulators of neural, immune and metabolic circuits along the microbiota\u2013gut\u2013brain axis; their targeted manipulation and standardised metabolomic assessment could enable earlier diagnosis and precision microbiome-based interventions for AD, a promise that now warrants validation in large, longitudinal and mechanistically informed clinical studies.<\/jats:p>","DOI":"10.17305\/bb.2025.12921","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T22:00:32Z","timestamp":1754949632000},"page":"240-250","source":"Crossref","is-referenced-by-count":36,"title":["Gut microbial metabolites and the brain\u2013gut axis in Alzheimer\u2019s disease: A review"],"prefix":"10.17305","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2815-113X","authenticated-orcid":false,"given":"Xinchen","family":"Ji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianye","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dexi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6922","published-online":{"date-parts":[[2025,8,11]]},"container-title":["Biomolecules and Biomedicine"],"original-title":[],"link":[{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/12921\/3982","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/12921\/3982","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T22:02:38Z","timestamp":1759183358000},"score":1,"resource":{"primary":{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/view\/12921"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,11]]},"references-count":0,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,9,29]]}},"URL":"https:\/\/doi.org\/10.17305\/bb.2025.12921","relation":{},"ISSN":["2831-090X","2831-0896"],"issn-type":[{"value":"2831-090X","type":"electronic"},{"value":"2831-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2025,8,11]]}}}