{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:48:04Z","timestamp":1792025284957,"version":"4.4.0"},"reference-count":122,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a complex neurodegenerative disorder that can be caused by multiple factors, such as abnormal amyloid-beta (A\u03b2) deposition, pathological changes in Tau protein, lipid metabolism disorders, and oxidative stress. Recent studies have revealed the potential link between gut microbiota and AD, particularly the impact of gut microbiota and its derivatives on microglia. As immune cells in the central nervous system (CNS), microglia are involved in neuroinflammation and the regulation of cognitive function. Research indicates that the dysregulation of gut microbiota may affect the phenotype and function of microglia through various mechanisms, including direct metabolite action and indirect immune and neurotransmitter regulation. This article reviews the direct and indirect effects of gut microbiota and its derivatives on microglia, explores their role in the pathogenesis of AD, and discusses therapeutic strategies based on gut microbiota, such as dietary regulation, probiotics, fecal microbiota transplantation, and traditional Chinese medicine. Although existing studies have shown the potential of these interventions, further research is needed to completely understand their application in the treatment of AD.<\/jats:p>","DOI":"10.3389\/fragi.2025.1704047","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T06:28:54Z","timestamp":1763706534000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["The gut\u2013brain axis in Alzheimer\u2019s disease: how gut microbiota modulate microglial function"],"prefix":"10.3389","volume":"6","author":[{"given":"Huan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhejianyi","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zedong","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xicai","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.3233\/JAD-215025","article-title":"Bifidobacterium breve prevents memory impairment through the reduction of both amyloid-\u03b2 production and microglia activation in app knock-in mouse","volume":"85","author":"Abdelhamid","year":"","journal-title":"J. Alzheimers Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2543","DOI":"10.3390\/nu14122543","article-title":"Probiotic Bifidobacterium breve MCC1274 mitigates Alzheimer\u2019s disease-related pathologies in wild-type mice","volume":"14","author":"Abdelhamid","year":"","journal-title":"Nutrients"},{"key":"B3","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.exger.2018.12.005","article-title":"Exercise and probiotics attenuate the development of Alzheimer's disease in transgenic mice: role of microbiome","volume":"115","author":"Abraham","year":"2019","journal-title":"Exp. Gerontol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut microbiota regulation of tryptophan metabolism in health and disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell host and Microbe"},{"key":"B5","doi-asserted-by":"publisher","first-page":"3656","DOI":"10.1099\/ijsem.0.001195","article-title":"Agathobaculum butyriciproducens gen. nov. sp. nov., a strict anaerobic, butyrate-producing gut bacterium isolated from human faeces and reclassification of Eubacterium desmolans as Agathobaculum desmolans comb. nov","volume":"66","author":"Ahn","year":"2016","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/s0165-3806(02)00537-0","article-title":"Transport of 14C-\u03b3-aminobutyric acid into brain, cerebrospinal fluid and choroid plexus in neonatal and adult rats","volume":"139","author":"Al-Sarraf","year":"2002","journal-title":"Dev. Brain Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2580","DOI":"10.1073\/pnas.0915139107","article-title":"Inhibitory role for GABA in autoimmune inflammation","volume":"107","author":"Bhat","year":"2010","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"650971","DOI":"10.3389\/fnins.2021.650971","article-title":"Therapeutic potential of vagus nerve stimulation for inflammatory bowel diseases","volume":"15","author":"Bonaz","year":"2021","journal-title":"Front. Neurosci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1038\/s41586-018-0119-x","article-title":"Microglial control of astrocytes in response to microbial metabolites","volume":"557","author":"Borucki","year":"2018","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s13024-024-00722-y","article-title":"The endotoxin hypothesis of Alzheimer\u2019s disease","volume":"19","author":"Brown","year":"2024","journal-title":"Mol. Neurodegener."},{"key":"B11","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/s11357-020-00257-2","article-title":"The gut microbiome\u2013derived metabolite trimethylamine N-oxide modulates neuroinflammation and cognitive function with aging","volume":"43","author":"Brunt","year":"2021","journal-title":"GeroScience"},{"key":"B12","doi-asserted-by":"publisher","first-page":"258","DOI":"10.13422\/j.cnki.syfjx.20232437","article-title":"Research progress of traditional Chinese medicine and its effective ingredients in the treatment of Alzheimer's disease","volume":"30","author":"Cao","year":"2024","journal-title":"Chin. J. Exp. Formulae"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1136\/gutjnl-2021-326269","article-title":"Gut microbiota regulate Alzheimer\u2019s disease pathologies and cognitive disorders via PUFA-associated neuroinflammation","volume":"71","author":"Chen","year":"2022","journal-title":"Gut"},{"key":"B14","doi-asserted-by":"publisher","first-page":"111499","DOI":"10.1016\/j.nut.2021.111499","article-title":"Multiple roles of short-chain fatty acids in Alzheimer disease","volume":"93","author":"Chen H.","year":"2022","journal-title":"Nutrition"},{"key":"B15","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/s41586-023-05788-0","article-title":"Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy","volume":"615","author":"Chen","year":"2023","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e1534","DOI":"10.1016\/S2214-109X(24)00264-X","article-title":"The global macroeconomic burden of Alzheimer's disease and other dementias: estimates and projections for 152 countries or territories","volume":"12","author":"Chen","year":"2024","journal-title":"Lancet Glob. Health"},{"key":"B17","doi-asserted-by":"publisher","first-page":"755925","DOI":"10.3389\/fcimb.2021.755925","article-title":"Porphyromonas gingivalis-induced cognitive impairment is associated with gut dysbiosis, neuroinflammation, and glymphatic dysfunction","volume":"11","author":"Chi","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2389319","DOI":"10.1080\/19490976.2024.2389319","article-title":"Age-associated temporal decline in butyrate-producing bacteria plays a key pathogenic role in the onset and progression of neuropathology and memory deficits in 3\u00d7 Tg-AD mice","volume":"16","author":"Chilton","year":"2024","journal-title":"Gut Microbes"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2371950","DOI":"10.1080\/19490976.2024.2371950","article-title":"Implications of microbe-derived \u0263-aminobutyric acid (GABA) in gut and brain barrier integrity and GABAergic signaling in Alzheimer\u2019s disease","volume":"16","author":"Conn","year":"2024","journal-title":"Gut Microbes"},{"key":"B20","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1038\/s41582-022-00697-8","article-title":"The role of the gut microbiota in multiple sclerosis","volume":"18","author":"Correale","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"B21","article-title":"Plasma proteomic associations with alzheimer\u2019s disease endophenotypes","author":"Dammer","year":"2025"},{"key":"B22","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.semcdb.2023.02.004","article-title":"The gut-brain axis and cognitive control: a role for the vagus nerve","volume":"156","author":"D\u00e9carie-Spain","year":"2024","journal-title":"Seminars Cell and Dev. Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1016\/j.tim.2021.04.003","article-title":"Bacterial outer membrane vesicles and host cell death signaling","volume":"29","author":"Dhital","year":"2021","journal-title":"Trends Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"10323","DOI":"10.1039\/d4fo02075h","article-title":"Lactiplantibacillus plantarum HEAL9 attenuates cognitive impairment and progression of Alzheimer's disease and related bowel symptoms in SAMP8 mice by modulating microbiota-gut-inflammasome-brain axis","volume":"15","author":"Di Salvo","year":"2024","journal-title":"Food and Funct."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.3390\/microorganisms10091838","article-title":"Gut bacteria and neurotransmitters","volume":"10","author":"Dicks","year":"2022","journal-title":"Microorganisms"},{"key":"B26","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/nrgastro.2016.200","article-title":"Gut-brain axis in 2016: brain-gut-microbiota axis - mood, metabolism and behaviour","volume":"14","author":"Dinan","year":"2017","journal-title":"Nat. Rev. Gastroenterology and Hepatology"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1859812","DOI":"10.1080\/19490976.2020.1859812","article-title":"The aryl hydrocarbon receptor as a mediator of host-microbiota interplay","volume":"12","author":"Dong","year":"2020","journal-title":"Gut Microbes"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e70601","DOI":"10.1096\/fj.202403117RR","article-title":"Chronic lipopolysaccharide exposure causes AD\u2010like pathology in Male mice with intact blood\u2013brain barrier","volume":"39","author":"Eid","year":"2025","journal-title":"FASEB J."},{"key":"B29","doi-asserted-by":"publisher","first-page":"3204","DOI":"10.3390\/nu15143204","article-title":"Dietary patterns and Alzheimer\u2019s disease: an updated review linking nutrition to neuroscience","volume":"15","author":"Ellouze","year":"2023","journal-title":"Nutrients"},{"key":"B30","doi-asserted-by":"publisher","first-page":"2260","DOI":"10.1016\/j.cmet.2021.10.010","article-title":"Microbiota-derived acetate enables the metabolic fitness of the brain innate immune system during health and disease","volume":"33","author":"Erny","year":"2021","journal-title":"Cell Metab."},{"key":"B31","doi-asserted-by":"publisher","first-page":"57","DOI":"10.2174\/1874285801610010057","article-title":"Suppl-1, M3: isolation, detection, and characterization of enterotoxigenic bacteroides fragilis in clinical samples","volume":"10","author":"Fathi","year":"2016","journal-title":"Open Microbiol. J."},{"key":"B32","doi-asserted-by":"publisher","first-page":"eabo2984","DOI":"10.1126\/scitranslmed.abo2984","article-title":"Gut microbiome composition may be an indicator of preclinical Alzheimer\u2019s disease","volume":"15","author":"Ferreiro","year":"2023","journal-title":"Sci. Transl. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3389\/fcimb.2018.00013","article-title":"Impact of the gut microbiota on intestinal immunity mediated by tryptophan metabolism","volume":"8","author":"Gao","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.jalz.2019.01.010","article-title":"2019 Alzheimer's disease facts and figures","volume":"15","author":"Gaugler","year":"2019","journal-title":"Alzheimers and Dementia"},{"key":"B35","doi-asserted-by":"publisher","first-page":"495","DOI":"10.3233\/JAD-170485","article-title":"Kynurenine pathway metabolites in Alzheimer\u2019s disease","volume":"60","author":"Giil","year":"2017","journal-title":"J. Alzheimer's Dis."},{"key":"B36","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1002\/glia.22772","article-title":"Serotonin stimulates secretion of exosomes from microglia cells","volume":"63","author":"Glebov","year":"2015","journal-title":"Glia"},{"key":"B37","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.nutres.2020.12.010","article-title":"Human gut microbiota Agathobaculum butyriciproducens improves cognitive impairment in LPS-induced and APP\/PS1 mouse models of Alzheimer's disease","volume":"86","author":"Go","year":"2021","journal-title":"Nutr. Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"4010","DOI":"10.1021\/acschemneuro.4c00370","article-title":"Propionate decreases microglial activation but impairs phagocytic capacity in response to aggregated fibrillar amyloid beta protein","volume":"15","author":"Gold","year":"2024","journal-title":"ACS Chem. Neurosci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"925435","DOI":"10.3389\/fcimb.2022.925435","article-title":"Outer membrane vesicles of Porphyromonas gingivalis trigger NLRP3 inflammasome and induce neuroinflammation, tau phosphorylation, and memory dysfunction in mice","volume":"12","author":"Gong","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.1007\/s00213-019-05265-5","article-title":"Do your gut microbes affect your brain dopamine?","volume":"236","author":"Gonz\u00e1lez-Arancibia","year":"2019","journal-title":"Psychopharmacology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1056\/NEJMoa1211851","article-title":"TREM2 variants in Alzheimer's disease","volume":"368","author":"Guerreiro","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1515\/tnsci-2020-0203","article-title":"Effects of gut microbiota and probiotics on Alzheimer\u2019s disease","volume":"12","author":"Guo","year":"2021","journal-title":"Transl. Neurosci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"13412","DOI":"10.1096\/fj.201901575R","article-title":"Extracellular RNAs in periodontopathogenic outer membrane vesicles promote TNF-\u03b1 production in human macrophages and cross the blood\u2013brain barrier in mice","volume":"33","author":"Han","year":"2019","journal-title":"FASEB J."},{"key":"B44","doi-asserted-by":"publisher","first-page":"6213","DOI":"10.2147\/JIR.S384949","article-title":"Vagus nerve and underlying impact on the gut microbiota-brain axis in behavior and neurodegenerative diseases","volume":"15","author":"Han","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"0300060520925930","DOI":"10.1177\/0300060520925930","article-title":"Rapid improvement in Alzheimer\u2019s disease symptoms following fecal microbiota transplantation: a case report","volume":"48","author":"Hazan","year":"2020","journal-title":"J. Int. Med. Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"5001","DOI":"10.1038\/s41380-025-03156-0","article-title":"Key questions for the future of amyloid research in dementia: a framework for integrating complex datasets","volume":"30","author":"Hunter","year":"2025","journal-title":"Mol. Psychiatry"},{"key":"B47","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/nature20587","article-title":"Gamma frequency entrainment attenuates amyloid load and modifies microglia","volume":"540","author":"Iaccarino","year":"2016","journal-title":"Nature"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.1002\/med.21653","article-title":"Expert insights: the potential role of the gut microbiome\u2010bile acid\u2010brain axis in the development and progression of Alzheimer's disease and hepatic encephalopathy","volume":"40","author":"Jia","year":"2020","journal-title":"Med. Res. Rev."},{"key":"B49","doi-asserted-by":"publisher","first-page":"3951","DOI":"10.1038\/s41380-025-02973-7","article-title":"Metagenomic analysis characterizes stage-specific gut microbiota in Alzheimer\u2019s disease","volume":"30","author":"Jia","year":"2025","journal-title":"Mol. Psychiatry"},{"key":"B50","doi-asserted-by":"publisher","first-page":"109452","DOI":"10.1016\/j.cbi.2021.109452","article-title":"Sodium butyrate ameliorates the impairment of synaptic plasticity by inhibiting the neuroinflammation in 5XFAD mice","volume":"341","author":"Jiang","year":"2021","journal-title":"Chemico-biological Interact."},{"key":"B51","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1056\/NEJMoa1211103","article-title":"Variant of TREM2 associated with the risk of Alzheimer's disease","volume":"368","author":"Jonsson","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"e0003222","DOI":"10.1128\/mmbr.00032-22","article-title":"Outer membrane vesicles: biogenesis, functions, and issues","volume":"86","author":"Juodeikis","year":"2022","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"B53","doi-asserted-by":"publisher","first-page":"e70417","DOI":"10.1002\/alz.70417","article-title":"Gut microbiome compositional and functional features associate with Alzheimer's disease pathology","volume":"21","author":"Kang","year":"2025","journal-title":"Alzheimer's and Dementia"},{"key":"B54","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1038\/s41577-025-01188-9","article-title":"A role for microglia in mediating the microbiota\u2013gut\u2013brain axis","volume":"25","author":"Keane","year":"2025","journal-title":"Nat. Rev. Immunol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"118627","DOI":"10.1016\/j.lfs.2020.118627","article-title":"Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease","volume":"264","author":"Kesika","year":"2021","journal-title":"Life Sci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"4186","DOI":"10.1111\/jam.15533","article-title":"Interactive relationship between Trp metabolites and gut microbiota: the impact on human pathology of disease","volume":"132","author":"Khoshnevisan","year":"2022","journal-title":"J. Appl. Microbiol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"2505","DOI":"10.1177\/0271678X19899577","article-title":"Metabolic endotoxemia promotes neuroinflammation after focal cerebral ischemia","volume":"40","author":"Kurita","year":"2020","journal-title":"J. Cereb. Blood Flow and Metabolism"},{"key":"B58","doi-asserted-by":"publisher","first-page":"106908","DOI":"10.1016\/j.intimp.2020.106908","article-title":"GABA-mediated activated microglia induce neuroinflammation in the hippocampus of mice following cold exposure through the NLRP3 inflammasome and NF-\u03baB signaling pathways","volume":"89","author":"Lang","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1800359","DOI":"10.1002\/mnfr.201800359","article-title":"Lactobacillus plantarum C29\u2010fermented soybean (DW2009) alleviates memory impairment in 5XFAD transgenic mice by regulating microglia activation and gut microbiota composition","volume":"62","author":"Lee","year":"2018","journal-title":"Mol. Nutr. and Food Res."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1582119","DOI":"10.3389\/fimmu.2025.1582119","article-title":"Gut Microbiota-driven neuroinflammation in Alzheimer's disease: from mechanisms to therapeutic opportunities","volume":"16","author":"Lei","year":"2025","journal-title":"Front. Immunol."},{"key":"B61","doi-asserted-by":"crossref","DOI":"10.21203\/rs.3.rs-3130204\/v1","article-title":"The effectiveness and mechanisms of acupuncture in treating Alzheimer's disease","author":"Li","year":"2023"},{"key":"B62","doi-asserted-by":"publisher","first-page":"e14704","DOI":"10.1111\/cns.14704","article-title":"Deciphering the intricate linkage between the gut microbiota and Alzheimer's disease: elucidating mechanistic pathways promising therapeutic strategies","volume":"30","author":"Liang","year":"2024","journal-title":"CNS Neurosci. and Ther."},{"key":"B63","doi-asserted-by":"publisher","first-page":"634069","DOI":"10.3389\/fcell.2020.634069","article-title":"Structural and functional dysbiosis of fecal microbiota in Chinese patients with Alzheimer's disease","volume":"8","author":"Ling","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"7152","DOI":"10.1021\/acs.jafc.0c02807","article-title":"Anti-neuroinflammatory effect of short-chain fatty acid acetate against Alzheimer\u2019s disease via upregulating GPR41 and inhibiting ERK\/JNK\/NF-\u03baB","volume":"68","author":"Liu","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"B65","doi-asserted-by":"publisher","first-page":"70","DOI":"10.31083\/j.jin2203070","article-title":"Maturation, morphology, and function: the decisive role of intestinal flora on microglia: a review","volume":"22","author":"Liu","year":"2023","journal-title":"J. Integr. Neurosci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/B978-0-12-804766-8.00013-3","article-title":"Alzheimer's disease","volume":"167","author":"Lopez","year":"2019","journal-title":"Handb. Clin. Neurology"},{"key":"B67","doi-asserted-by":"publisher","first-page":"e13286","DOI":"10.1111\/acel.13286","article-title":"Antiallergic drug desloratadine as a selective antagonist of 5HT2A receptor ameliorates pathology of Alzheimer's disease model mice by improving microglial dysfunction","volume":"20","author":"Lu","year":"2021","journal-title":"Aging Cell"},{"key":"B68","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.3389\/fmicb.2016.01544","article-title":"Bacteroides fragilis lipopolysaccharide and inflammatory signaling in Alzheimer\u2019s disease","volume":"7","author":"Lukiw","year":"2016","journal-title":"Front. Microbiol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"111116","DOI":"10.1016\/j.isci.2024.111116","article-title":"Gut commensal Agathobacter rectalis alleviates microglia-mediated neuroinflammation against pathogenesis of Alzheimer disease","volume":"27","author":"Lv","year":"2024","journal-title":"iScience"},{"key":"B70","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1111\/cns.13620","article-title":"Microglial\/Macrophage polarization and function in brain injury and repair after stroke","volume":"27","author":"Lyu","year":"2021","journal-title":"CNS Neurosci. and Ther."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1080\/19490976.2020.1758008","article-title":"Host\u2013microbiome interactions: the aryl hydrocarbon receptor as a critical node in tryptophan metabolites to brain signaling","volume":"11","author":"Ma","year":"2020","journal-title":"Gut Microbes"},{"key":"B72","doi-asserted-by":"publisher","first-page":"107361","DOI":"10.1016\/j.phrs.2024.107361","article-title":"Gut microbiota-brain bile acid axis orchestrates aging-related neuroinflammation and behavior impairment in mice","volume":"208","author":"Ma","year":"2024","journal-title":"Pharmacol. Res."},{"key":"B73","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.jalz.2018.07.217","article-title":"Altered bile acid profile associates with cognitive impairment in Alzheimer's disease\u2014an emerging role for gut microbiome","volume":"15","author":"MahmoudianDehkordi","year":"2019","journal-title":"Alzheimer's and Dementia"},{"key":"B74","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.ejim.2004.05.008","article-title":"Helicobacter pylori and Alzheimer's disease: a possible link","volume":"15","author":"Malaguarnera","year":"2004","journal-title":"Eur. J. Intern. Med."},{"key":"B75","doi-asserted-by":"publisher","first-page":"796288","DOI":"10.3389\/fimmu.2022.796288","article-title":"Gut microbiota interact with the brain through systemic chronic inflammation: implications on neuroinflammation, neurodegeneration, and aging","volume":"13","author":"Mou","year":"2022","journal-title":"Front. Immunol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.ebiom.2019.08.032","article-title":"Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer's disease markers in subjects with mild cognitive impairment","volume":"47","author":"Nagpal","year":"2019","journal-title":"EBioMedicine"},{"key":"B77","doi-asserted-by":"publisher","first-page":"e17333","DOI":"10.7759\/cureus.17333","article-title":"Predictors of hospitalization for manic episode in Alzheimer's dementia: inputs from an inpatient case-control study","volume":"13","author":"Nandwana","year":"2021","journal-title":"Cureus"},{"key":"B78","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3390\/nu14010020","article-title":"Probiotics for Alzheimer\u2019s disease: a systematic review","volume":"14","author":"Naomi","year":"2021","journal-title":"Nutrients"},{"key":"B79","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1038\/nm.3407","article-title":"Development, maintenance and disruption of the blood-brain barrier","volume":"19","author":"Obermeier","year":"2013","journal-title":"Nat. Med."},{"key":"B80","doi-asserted-by":"publisher","first-page":"2300601","DOI":"10.1002\/mnfr.202300601","article-title":"A high\u2010tryptophan diet alleviated cognitive impairment and neuroinflammation in APP\/PS1 mice through activating aryl hydrocarbon receptor via the regulation of gut microbiota","volume":"68","author":"Pan","year":"2024","journal-title":"Mol. Nutr. and Food Res."},{"key":"B81","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1007\/s00401-018-1856-5","article-title":"Interplay among gut microbiota, intestinal mucosal barrier and enteric neuro-immune system: a common path to neurodegenerative diseases?","volume":"136","author":"Pellegrini","year":"2018","journal-title":"Acta Neuropathol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"6684","DOI":"10.1007\/s12035-022-02990-5","article-title":"The role of a gut microbial-derived metabolite, trimethylamine N-oxide (TMAO), in neurological disorders","volume":"59","author":"Praveenraj","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"2282790","DOI":"10.1080\/19490976.2023.2282790","article-title":"Multi-omics data reveals aberrant gut microbiota-host glycerophospholipid metabolism in association with neuroinflammation in APP\/PS1 mice","volume":"15","author":"Qian","year":"2023","journal-title":"Gut Microbes"},{"key":"B84","doi-asserted-by":"publisher","first-page":"127858","DOI":"10.1016\/j.micres.2024.127858","article-title":"Gut microbiota modulates neurotransmitter and gut-brain signaling","volume":"287","author":"Qu","year":"2024","journal-title":"Microbiol. Res."},{"key":"B85","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1038\/s41582-025-01123-5","article-title":"Amyloid-lowering immunotherapies for Alzheimer disease: current status and future directions","volume":"21","author":"Rafii","year":"2025","journal-title":"Nat. Rev. Neurol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1038\/nm.4106","article-title":"Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor","volume":"22","author":"Rothhammer","year":"2016","journal-title":"Nat. Med."},{"key":"B87","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1146\/annurev-micro-052821-031444","article-title":"Bacterial outer membrane vesicles: from discovery to applications","volume":"75","author":"Sartorio","year":"2021","journal-title":"Annu. Rev. Microbiol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer's disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"B89","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1038\/nm.4185","article-title":"Signals from the gut microbiota to distant organs in physiology and disease","volume":"22","author":"Schroeder","year":"2016","journal-title":"Nat. Med."},{"key":"B90","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.cell.2016.01.013","article-title":"Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans","volume":"164","author":"Sender","year":"2016","journal-title":"Cell"},{"key":"B91","doi-asserted-by":"publisher","first-page":"112400","DOI":"10.1016\/j.exger.2024.112400","article-title":"Effect of outer membrane vesicles of Lactobacillus pentosus on Tau phosphorylation and CDK5-Calpain pathway in mice","volume":"189","author":"Shao","year":"2024","journal-title":"Exp. Gerontol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"eadx0043","DOI":"10.1126\/science.adx0043","article-title":"Neuroinflammation across neurological diseases","volume":"388","author":"Shi","year":"2025","journal-title":"Science"},{"key":"B93","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/s0361-9230(01)00755-9","article-title":"Evidence that nitric oxide production increases \u03b3-amino butyric acid permeability of blood-brain barrier","volume":"57","author":"Shyamaladevi","year":"2002","journal-title":"Brain Res. Bull."},{"key":"B94","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1186\/s12974-019-1632-z","article-title":"Stress-induced microglial activation occurs through \u03b2-adrenergic receptor: noradrenaline as a key neurotransmitter in microglial activation","volume":"16","author":"Sugama","year":"2019","journal-title":"J. Neuroinflammation"},{"key":"B95","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/s41398-019-0525-3","article-title":"Fecal microbiota transplantation alleviated Alzheimer\u2019s disease-like pathogenesis in APP\/PS1 transgenic mice","volume":"9","author":"Sun","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"B96","first-page":"3323","article-title":"Research progress of traditional Chinese medicine in the treatment of Alzheimer's disease","volume":"19","author":"Sun","year":"2019","journal-title":"J. Integr. Chin. West. Med. Cardio-Cerebrovascular Dis."},{"key":"B97","doi-asserted-by":"publisher","first-page":"1900636","DOI":"10.1002\/mnfr.201900636","article-title":"Effect of Clostridium butyricum against microglia\u2010mediated neuroinflammation in Alzheimer's disease via regulating gut microbiota and metabolites butyrate","volume":"64","author":"Sun J.","year":"2020","journal-title":"Mol. Nutr. and Food Res."},{"key":"B98","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1080\/10408398.2019.1598334","article-title":"Tryptophan (Trp) modulates gut homeostasis via aryl hydrocarbon receptor (AhR)","volume":"60","author":"Sun","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"B99","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.bbi.2022.08.003","article-title":"Microbiota-derived metabolite indoles induced aryl hydrocarbon receptor activation and inhibited neuroinflammation in APP\/PS1 mice","volume":"106","author":"Sun","year":"2022","journal-title":"Brain, Behav. Immun."},{"key":"B100","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1097\/00004647-200110000-00012","article-title":"GAT2\/BGT-1 as a system responsible for the transport of \u03b3-aminobutyric acid at the mouse blood\u2013brain barrier","volume":"21","author":"Takanaga","year":"2001","journal-title":"J. Cereb. Blood Flow and Metabolism"},{"key":"B101","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1016\/j.chom.2022.05.005","article-title":"Gut bacterial isoamylamine promotes age-related cognitive dysfunction by promoting microglial cell death","volume":"30","author":"Teng","year":"2022","journal-title":"Cell Host and Microbe"},{"key":"B102","first-page":"115","article-title":"Detection of neurotransmitter amines in microorganisms with the use of high-performance liquid chromatography","volume":"372","author":"Tsavkelova","year":"2000","journal-title":"Dokl. Biochem."},{"key":"B103","doi-asserted-by":"publisher","first-page":"3091","DOI":"10.3390\/ijms23063091","article-title":"Helicobacter pylori urease: potential contributions to Alzheimer\u2019s disease","volume":"23","author":"Uberti","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B104","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/j.1365-2249.2008.03713.x","article-title":"Allergy and the gastrointestinal system","volume":"153","author":"Vighi","year":"2008","journal-title":"Clin. and Exp. Immunol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1038\/s41422-019-0216-x","article-title":"Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer\u2019s disease progression","volume":"29","author":"Wang","year":"2019","journal-title":"Cell Res."},{"key":"B106","doi-asserted-by":"publisher","first-page":"106354","DOI":"10.1016\/j.intimp.2020.106354","article-title":"5-HT1AR alleviates A\u03b2-induced cognitive decline and neuroinflammation through crosstalk with NF-\u03baB pathway in mice","volume":"82","author":"Wang","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"B107","doi-asserted-by":"publisher","first-page":"116549","DOI":"10.1016\/j.biopha.2024.116549","article-title":"Trimethylamine-N-oxide aggravated the sympathetic excitation in D-galactose induced aging rats by down-regulating P2Y12 receptor in microglia","volume":"174","author":"Wang","year":"2024","journal-title":"Biomed. and Pharmacother."},{"key":"B108","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s13024-025-00857-6","article-title":"Alzheimer\u2019s disease pathogenesis: standing at the crossroad of lipid metabolism and immune response","volume":"20","author":"Wang","year":"2025","journal-title":"Mol. Neurodegener."},{"key":"B109","doi-asserted-by":"publisher","first-page":"3872","DOI":"10.1038\/s41467-024-47683-w","article-title":"Bacteroidota inhibit microglia clearance of amyloid-beta and promote plaque deposition in Alzheimer\u2019s disease mouse models","volume":"15","author":"Was\u00e9n","year":"2024","journal-title":"Nat. Commun."},{"key":"B110","doi-asserted-by":"publisher","first-page":"103493","DOI":"10.1016\/j.mcn.2020.103493","article-title":"Short-chain fatty acids (SCFAs) alone or in combination regulate select immune functions of microglia-like cells","volume":"105","author":"Wenzel","year":"2020","journal-title":"Mol. Cell. Neurosci."},{"key":"B111","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1038\/s41588-021-00921-z","article-title":"A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer\u2019s disease","volume":"53","author":"Wightman","year":"2021","journal-title":"Nat. Genet."},{"key":"B112","doi-asserted-by":"publisher","first-page":"e10262","DOI":"10.7717\/peerj.10262","article-title":"Treatment with bifidobacteria can suppress A\u03b2 accumulation and neuroinflammation in APP\/PS1 mice","volume":"8","author":"Wu","year":"2020","journal-title":"PeerJ"},{"key":"B113","doi-asserted-by":"publisher","first-page":"5471","DOI":"10.1038\/s41467-023-41283-w","article-title":"Bacteroides Fragilis in the gut microbiomes of Alzheimer\u2019s disease activates microglia and triggers pathogenesis in neuronal C\/EBP\u03b2 transgenic mice","volume":"14","author":"Xia","year":"2023","journal-title":"Nat. Commun."},{"key":"B114","doi-asserted-by":"publisher","first-page":"12306","DOI":"10.1002\/jev2.12306","article-title":"Helicobacter pylori\u2010derived outer membrane vesicles contribute to Alzheimer's disease pathogenesis via C3\u2010C3aR signalling","volume":"12","author":"Xie","year":"2023","journal-title":"J. Extracell. Vesicles"},{"key":"B115","doi-asserted-by":"publisher","first-page":"e70091","DOI":"10.1111\/cns.70091","article-title":"The gut microbiota modulates neuroinflammation in Alzheimer's disease: elucidating crucial factors and mechanistic underpinnings","volume":"30","author":"Yang","year":"2024","journal-title":"CNS Neurosci. and Ther."},{"key":"B116","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1016\/j.immuni.2017.05.011","article-title":"The enteric network: interactions between the immune and nervous systems of the gut","volume":"46","author":"Yoo","year":"2017","journal-title":"Immunity"},{"key":"B117","doi-asserted-by":"publisher","first-page":"585","DOI":"10.3233\/JAD-220413","article-title":"Trimethylamine N-oxide reduces neurite density and plaque intensity in a murine model of Alzheimer\u2019s disease","volume":"90","author":"Zarbock","year":"2022","journal-title":"J. Alzheimer's Dis."},{"key":"B118","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/s41392-024-01911-3","article-title":"Recent advances in Alzheimer\u2019s disease: mechanisms, clinical trials and new drug development strategies","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"B119","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s13024-025-00812-5","article-title":"Peripheral and central neuroimmune mechanisms in Alzheimer\u2019s disease pathogenesis","volume":"20","author":"Zhang","year":"2025","journal-title":"Mol. Neurodegener."},{"key":"B120","doi-asserted-by":"publisher","first-page":"9100","DOI":"10.1007\/s12035-018-1015-y","article-title":"Bacteroidetes neurotoxins and inflammatory neurodegeneration","volume":"55","author":"Zhao","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"B121","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1038\/s41422-022-00645-7","article-title":"Gut microbiota drives macrophage-dependent self-renewal of intestinal stem cells via niche enteric serotonergic neurons","volume":"32","author":"Zhu","year":"2022","journal-title":"Cell Res."},{"key":"B122","doi-asserted-by":"publisher","first-page":"4646","DOI":"10.1021\/acs.jafc.3c00652","article-title":"Bifidobacterium breve HNXY26M4 attenuates cognitive deficits and neuroinflammation by regulating the gut\u2013brain axis in APP\/PS1 mice","volume":"71","author":"Zhu","year":"2023","journal-title":"J. Agric. Food Chem."}],"container-title":["Frontiers in Aging"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fragi.2025.1704047\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T06:28:57Z","timestamp":1763706537000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fragi.2025.1704047\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,21]]},"references-count":122,"alternative-id":["10.3389\/fragi.2025.1704047"],"URL":"https:\/\/doi.org\/10.3389\/fragi.2025.1704047","relation":{},"ISSN":["2673-6217"],"issn-type":[{"value":"2673-6217","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,21]]},"article-number":"1704047"}}