{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T22:07:40Z","timestamp":1788559660792,"version":"build-2803163510"},"reference-count":88,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"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. Microbiol."],"abstract":"<jats:p>The pathogenesis of neurodegenerative diseases (NDDs) such as Alzheimer\u2019s disease (AD) and Parkinson\u2019s disease (PD) is very complex. Recent studies have shown that gut microbiota and their metabolites play a key role in the progression of these diseases. Tryptophan (Trp) is an essential amino acid, which mainly produces a variety of biologically active compounds in the intestine through the metabolism of indole pathway, Kynurenine pathway (KP) and serotonin pathway, including indole derivatives, Kynurenine (KYN) and serotonin (5-HT). These metabolites affect the central nervous system (CNS) through the Microbiota-gut-brain axis (MGBA) and affect CNS in a variety of mechanisms, including immune regulation, neuroprotection and maintenance of intestinal barrier function. They are involved in key pathological processes such as neuroinflammation, oxidative stress and pathological protein aggregation. This paper systematically reviews the mechanism of the role of Trp metabolites derived from gut microbiota in NDDs, and explores their specific roles in AD, PD, Amyotrophic Lateral Sclerosis (ALS) and Huntington\u2019s disease (HD), and summarizes the potential therapeutic value of the current pathway strategy. These strategies include nutritional intervention, targeted microbiome therapy [such as probiotic and fecal microbiota transplantation (FMT)], and metabolite-derived drugs. Future research must clarify its dynamic mechanism in the human body, develop relevant biomarkers, and promote personalized prevention and treatment strategies through clinical transformation, so as to provide a new direction for early intervention and treatment of NDDs.<\/jats:p>","DOI":"10.3389\/fmicb.2026.1820111","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:47:50Z","timestamp":1779256070000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The microbiota-tryptophan-brain axis in neurodegenerative diseases: pathogenic mechanisms, disease-specific roles, and translational therapeutics"],"prefix":"10.3389","volume":"17","author":[{"given":"Ziyi","family":"Wang","sequence":"first","affiliation":[{"name":"The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou","place":["Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Li","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou","place":["Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Dong","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou","place":["Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Gansu Provincial Hospital, Lanzhou","place":["Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/nature18849","article-title":"Interactions between the microbiota and pathogenic bacteria in the gut.","volume":"535","author":"B\u00e4umler","year":"2016","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"6737","DOI":"10.3390\/ijms22136737","article-title":"The footprint of kynurenine pathway in neurodegeneration: janus-faced Role in Parkinson\u2019s disorder and therapeutic implications.","volume":"22","author":"Behl","year":"2021","journal-title":"Int. J. Mol. Sci"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1348551","DOI":"10.3389\/fnins.2024.1348551","article-title":"The impact of estradiol on serotonin, glutamate, and dopamine systems.","volume":"18","author":"Bendis","year":"2024","journal-title":"Front. Neurosci"},{"key":"B4","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.jneuroim.2017.06.007","article-title":"Estrogen protection against EAE modulates the microbiota and mucosal-associated regulatory cells.","volume":"310","author":"Benedek","year":"2017","journal-title":"J. Neuroimmunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","article-title":"Parkinson\u2019s disease.","volume":"397","author":"Bloem","year":"2021","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"100071","DOI":"10.1016\/j.pharmr.2025.100071","article-title":"Targeting the serotonergic system in the treatment of neurodegenerative diseases-emerging therapies and unmet challenges.","volume":"77","author":"Br\u00fcge","year":"2025","journal-title":"Pharmacol. Rev"},{"key":"B7","doi-asserted-by":"publisher","first-page":"6319","DOI":"10.1007\/s12035-017-0845-3","article-title":"Alternations of metabolic profile and kynurenine metabolism in the plasma of Parkinson\u2019s Disease.","volume":"55","author":"Chang","year":"2018","journal-title":"Mol. Neurobiol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e12786","DOI":"10.1111\/aji.12786","article-title":"The role of indoleamine-2,3-dioxygenase in normal and pathological pregnancies.","volume":"79","author":"Chang","year":"2018","journal-title":"Am. J. Reprod. Immunol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s43556-025-00307-1","article-title":"Microbiota-gut-brain axis in neurodegenerative diseases: molecular mechanisms and therapeutic targets.","volume":"6","author":"Chen","year":"2025","journal-title":"Mol. Biomed"},{"key":"B10","doi-asserted-by":"publisher","first-page":"74","DOI":"10.14336\/AD.2023.0524","article-title":"Brain-gut-microbiota axis in amyotrophic lateral sclerosis: a historical overview and future directions.","volume":"15","author":"Chen","year":"2024","journal-title":"Aging Dis"},{"key":"B11","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s40035-025-00506-4","article-title":"Glycosylation in neuroinflammation: mechanisms, implications, and therapeutic strategies for neurodegenerative diseases.","volume":"14","author":"Cheng","year":"2025","journal-title":"Transl. Neurodegener"},{"key":"B12","doi-asserted-by":"publisher","first-page":"107988","DOI":"10.1016\/j.pharmthera.2021.107988","article-title":"Gut dysbiosis, defective autophagy and altered immune responses in neurodegenerative diseases: tales of a vicious cycle.","volume":"231","author":"Chidambaram","year":"2022","journal-title":"Pharmacol. Ther"},{"key":"B13","doi-asserted-by":"publisher","first-page":"696","DOI":"10.3390\/antiox14060696","article-title":"Oxidative stress: pathological driver in chronic neurodegenerative diseases.","volume":"14","author":"Chong","year":"2025","journal-title":"Antioxidants"},{"key":"B14","doi-asserted-by":"publisher","first-page":"21937","DOI":"10.1074\/jbc.274.31.21937","article-title":"Potent neuroprotective properties against the Alzheimer beta-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid.","volume":"274","author":"Chyan","year":"1999","journal-title":"J. Biol. Chem"},{"key":"B15","doi-asserted-by":"publisher","first-page":"104729","DOI":"10.1016\/j.neubiorev.2022.104729","article-title":"The role of serotonin in declarative memory: a systematic review of animal and human research.","volume":"139","author":"Coray","year":"2022","journal-title":"Neurosci. Biobehav Rev"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1152\/physrev.00018.2018","article-title":"The microbiota-gut-brain axis.","volume":"99","author":"Cryan","year":"2019","journal-title":"Physiol. Rev"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2325","DOI":"10.1194\/jlr.R036012","article-title":"The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism.","volume":"54","author":"den Besten","year":"2013","journal-title":"J. Lipid Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.bbi.2015.04.004","article-title":"Gut microbiota depletion from early adolescence in mice: implications for brain and behaviour.","volume":"48","author":"Desbonnet","year":"2015","journal-title":"Brain Behav. Immun"},{"key":"B19","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1186\/s12964-025-02393-8","article-title":"Interactions between gut microbiota and Parkinson\u2019s disease: the role of tryptophan metabolism.","volume":"23","author":"Fan","year":"2025","journal-title":"Cell Commun. Signal"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1650807","DOI":"10.3389\/fnins.2025.1650807","article-title":"Akkermansia muciniphila in neurological disorders: mechanisms and therapeutic potential via the gut-brain axis.","volume":"19","author":"Feng","year":"2025","journal-title":"Front. Neurosci"},{"key":"B21","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1093\/advances\/nmz127","article-title":"Tryptophan metabolism: a link between the gut microbiota and brain.","volume":"11","author":"Gao","year":"2020","journal-title":"Adv. Nutr"},{"key":"B22","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1126\/science.aad9378","article-title":"How colonization by microbiota in early life shapes the immune system.","volume":"352","author":"Gensollen","year":"2016","journal-title":"Science"},{"key":"B23","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.jpba.2014.10.010","article-title":"Metabolite profiling for the identification of altered metabolic pathways in Alzheimer\u2019s disease.","volume":"107","author":"Gonz\u00e1lez-Dom\u00ednguez","year":"2015","journal-title":"J. Pharm. Biomed. Anal"},{"key":"B24","doi-asserted-by":"publisher","first-page":"101247","DOI":"10.1016\/j.yfrne.2026.101247","article-title":"The microbiota-gut-brain axis in Huntington\u2019s disease: evidence, mechanisms and therapeutic opportunities.","volume":"81","author":"Gu","year":"2026","journal-title":"Front. Neuroendocrinol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"299","DOI":"10.3233\/JAD-201040","article-title":"Gut microbiome features of chinese patients newly diagnosed with Alzheimer\u2019s disease or mild cognitive impairment.","volume":"80","author":"Guo","year":"2021","journal-title":"J. Alzheimers Dis"},{"key":"B26","doi-asserted-by":"publisher","first-page":"5208","DOI":"10.1021\/acs.jafc.4c08548","article-title":"Indole-3-propionic acid attenuates neuroinflammation and cognitive deficits by inhibiting the RAGE-JAK2-STAT3 signaling pathway.","volume":"73","author":"Hao","year":"2025","journal-title":"J. Agric. Food Chem"},{"key":"B27","doi-asserted-by":"publisher","first-page":"151","DOI":"10.3389\/fimmu.2018.00151","article-title":"The role of indoleamine-2,3-dioxygenase in cancer development, diagnostics, and therapy.","volume":"9","author":"Horny\u00e1k","year":"2018","journal-title":"Front. Immunol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1007\/s10571-025-01596-4","article-title":"Kynurenine pathway modulation by exercise in multiple sclerosis: implications for neuroprotection and inflammation.","volume":"45","author":"Hoseini","year":"2025","journal-title":"Cell Mol. Neurobiol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"0912","DOI":"10.34133\/research.0912","article-title":"Mitochondria metabolism regulates glucose-lipid homeostasis in neurodegenerative diseases.","volume":"8","author":"Huang","year":"2025","journal-title":"Research"},{"key":"B30","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1053\/j.gastro.2024.11.012","article-title":"Intestinal epithelial serotonin as a novel target for treating disorders of gut-brain interaction and mood.","volume":"168","author":"Hung","year":"2025","journal-title":"Gastroenterology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2915","DOI":"10.3390\/ijms25052915","article-title":"Microbiota, tryptophan and aryl hydrocarbon receptors as the target triad in Parkinson\u2019s Disease-A narrative review.","volume":"25","author":"Iwaniak","year":"2024","journal-title":"Int. J. Mol. Sci"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.4155\/fmc-2017-0070","article-title":"In silico discovery and therapeutic potential of IDO1 and TDO2 inhibitors.","volume":"9","author":"Jernigan","year":"2017","journal-title":"Future Med. Chem"},{"key":"B33","doi-asserted-by":"publisher","first-page":"3547","DOI":"10.1021\/acs.jproteome.7b00263","article-title":"Antibiotic treatment preventing necrotising enterocolitis alters urinary and plasma metabolomes in preterm pigs.","volume":"16","author":"Jiang","year":"2017","journal-title":"J. Proteome Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"14582","DOI":"10.3390\/ijms241914582","article-title":"The involvement of neuroinflammation in the onset and progression of Parkinson\u2019s disease.","volume":"24","author":"Jurcau","year":"2023","journal-title":"IJMS"},{"key":"B35","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1006\/exnr.2001.7755","article-title":"A bile acid protects against motor and cognitive deficits and reduces striatal degeneration in the 3-nitropropionic acid model of Huntington\u2019s disease.","volume":"171","author":"Keene","year":"2001","journal-title":"Exp. Neurol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"928","DOI":"10.3390\/cells8080928","article-title":"17\u03b2-Estradiol modulates SIRT1 and halts oxidative Stress-Mediated cognitive impairment in a male aging mouse model.","volume":"8","author":"Khan","year":"2019","journal-title":"Cells"},{"key":"B37","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/j.jcmgh.2019.01.004","article-title":"Modulation of gut microbiota composition by serotonin signaling influences intestinal immune response and susceptibility to colitis.","volume":"7","author":"Kwon","year":"2019","journal-title":"Cell Mol. Gastroenterol. Hepatol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"985378","DOI":"10.3389\/fimmu.2022.985378","article-title":"Tryptophan metabolism: mechanism-oriented therapy for neurological and psychiatric disorders.","volume":"13","author":"Li","year":"2022","journal-title":"Front. Immunol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1617690","DOI":"10.3389\/fnagi.2025.1617690","article-title":"Kynurenine pathway: a possible new mechanism for exercise in the prevention and treatment of Alzheimer\u2019s disease.","volume":"17","author":"Li","year":"2025","journal-title":"Front. Aging Neurosci"},{"key":"B40","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1002\/arch.20159","article-title":"Biochemical mechanisms leading to tryptophan 2,3-dioxygenase activation.","volume":"64","author":"Li","year":"2007","journal-title":"Arch. Insect. Biochem. Physiol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"eadw8410","DOI":"10.1126\/sciadv.adw8410","article-title":"Gut microbial-derived indole-3-propionate improves cognitive function in Alzheimer\u2019s disease.","volume":"11","author":"Li","year":"2025","journal-title":"Sci. Adv"},{"key":"B42","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s42523-024-00323-6","article-title":"Improvement of insulin sensitivity by dietary fiber consumption during late pregnant sows is associated with gut microbiota regulation of tryptophan metabolism.","volume":"6","author":"Li","year":"2024","journal-title":"Anim. Microbiome"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1080\/19490976.2020.1758008","article-title":"Host-microbiome 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":"B44","doi-asserted-by":"publisher","first-page":"1309075","DOI":"10.3389\/fnins.2024.1309075","article-title":"Slowing Alzheimer\u2019s disease progression through probiotic supplementation.","volume":"18","author":"Medeiros","year":"2024","journal-title":"Front. Neurosci"},{"key":"B45","doi-asserted-by":"publisher","first-page":"104750","DOI":"10.1016\/j.psyneuen.2020.104750","article-title":"The gut microbiota metabolite indole increases emotional responses and adrenal medulla activity in chronically stressed male mice.","volume":"119","author":"Mir","year":"2020","journal-title":"Psychoneuroendocrinology"},{"key":"B46","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s12035-025-05447-7","article-title":"Mechanistic interplay of gut microbiota and blood-brain barrier integrity in neurodegenerative diseases.","volume":"63","author":"Mohammad","year":"2025","journal-title":"Mol. Neurobiol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.phrs.2012.10.007","article-title":"Modulation of intestinal barrier by intestinal microbiota: pathological and therapeutic implications.","volume":"69","author":"Natividad","year":"2013","journal-title":"Pharmacol. Res"},{"key":"B48","doi-asserted-by":"publisher","first-page":"3387","DOI":"10.21873\/anticanres.12605","article-title":"The impact of indoleamine 2,3-dioxygenase (IDO) expression on stage III gastric cancer.","volume":"38","author":"Nishi","year":"2018","journal-title":"Anticancer Res"},{"key":"B49","doi-asserted-by":"publisher","first-page":"4200","DOI":"10.1523\/JNEUROSCI.5032-08.2009","article-title":"Interferon-gamma and tumor necrosis factor-alpha mediate the upregulation of indoleamine 2,3-dioxygenase and the induction of depressive-like behavior in mice in response to bacillus Calmette-Guerin.","volume":"29","author":"O\u2019Connor","year":"2009","journal-title":"J. Neurosci"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.3390\/jcm10061299","article-title":"Gut microbiota interaction with the central nervous system throughout life.","volume":"10","author":"Ojeda","year":"2021","journal-title":"J. Clin. Med"},{"key":"B51","doi-asserted-by":"publisher","first-page":"12553","DOI":"10.1073\/pnas.93.22.12553","article-title":"Hydrogen peroxide-mediated neuronal cell death induced by an endogenous neurotoxin, 3-hydroxykynurenine.","volume":"93","author":"Okuda","year":"1996","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"B52","doi-asserted-by":"publisher","first-page":"3628","DOI":"10.3390\/molecules30173628","article-title":"Microbiota-derived tryptophan metabolite indole-3-propionic acid-emerging role in neuroprotection.","volume":"30","author":"Owe-Larsson","year":"2025","journal-title":"Molecules"},{"key":"B53","doi-asserted-by":"publisher","first-page":"e2300601","DOI":"10.1002\/mnfr.202300601","article-title":"A high-tryptophan 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. Food Res"},{"key":"B54","doi-asserted-by":"publisher","first-page":"105403","DOI":"10.1016\/j.nbd.2021.105403","article-title":"Indoles as essential mediators in the gut-brain axis. Their role in Alzheimer\u2019s disease.","volume":"156","author":"Pappolla","year":"2021","journal-title":"Neurobiol. Dis"},{"key":"B55","doi-asserted-by":"publisher","first-page":"853","DOI":"10.3390\/ijms25020853","article-title":"The influence of kynurenine metabolites on neurodegenerative pathologies.","volume":"25","author":"Pathak","year":"2024","journal-title":"Int. J. Mol. Sci"},{"key":"B56","doi-asserted-by":"publisher","first-page":"22448","DOI":"10.1021\/acs.jafc.5c08004","article-title":"Diosmetin alleviates cerebral ischemia\/reperfusion injury by modulating tryptophan metabolism through the microbiota-gut-brain axis.","volume":"73","author":"Peng","year":"2025","journal-title":"J. Agric. Food Chem"},{"key":"B57","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.neuroscience.2007.05.033","article-title":"Dopamine receptor activation reveals a novel, kynurenate-sensitive component of striatal N-methyl-D-aspartate neurotoxicity.","volume":"148","author":"Poeggeler","year":"2007","journal-title":"Neuroscience"},{"key":"B58","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1111\/bpa.12426","article-title":"Huntington\u2019s disease (HD): the neuropathology of a multisystem neurodegenerative disorder of the human brain.","volume":"26","author":"R\u00fcb","year":"2016","journal-title":"Brain Pathol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"4269","DOI":"10.1007\/s12035-020-01961-y","article-title":"The microbiota-gut-immune-glia (MGIG) axis in major depression.","volume":"57","author":"Rudzki","year":"2020","journal-title":"Mol. Neurobiol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s13024-025-00851-y","article-title":"RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.","volume":"20","author":"Rummens","year":"2025","journal-title":"Mol. Neurodegener"},{"key":"B61","doi-asserted-by":"publisher","first-page":"5646","DOI":"10.3390\/ijms21165646","article-title":"Proteotoxicity and neurodegenerative diseases.","volume":"21","author":"Ruz","year":"2020","journal-title":"Int. J. Mol. Sci"},{"key":"B62","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/s00109-023-02289-5","article-title":"Activation of aryl hydrocarbon receptor (AhR) in Alzheimer\u2019s disease: role of tryptophan metabolites generated by gut host-microbiota.","volume":"101","author":"Salminen","year":"2023","journal-title":"J. Mol. Med."},{"key":"B63","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/s41575-019-0173-3","article-title":"Probiotics and prebiotics in intestinal health and disease: from biology to the clinic.","volume":"16","author":"Sanders","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease.","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"B65","doi-asserted-by":"publisher","first-page":"111473","DOI":"10.1016\/j.brainresbull.2025.111473","article-title":"Gut microbiota dysbiosis and disturbed tryptophan metabolism mediate cognitive impairment in mice with circadian rhythm disruption.","volume":"229","author":"Song","year":"2025","journal-title":"Brain Res. Bull"},{"key":"B66","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":"B67","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.bbi.2018.02.005","article-title":"Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson\u2019s disease mice: gut microbiota, glial reaction and TLR4\/TNF-\u03b1 signaling pathway.","volume":"70","author":"Sun","year":"2018","journal-title":"Brain Behav. Immun"},{"key":"B68","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1097\/WCO.0000000000000599","article-title":"Neuroinflammatory mechanisms in amyotrophic lateral sclerosis pathogenesis.","volume":"31","author":"Thonhoff","year":"2018","journal-title":"Curr. Opin. Neurol"},{"key":"B69","doi-asserted-by":"publisher","first-page":"7230","DOI":"10.1007\/s12035-025-04708-9","article-title":"Role of probiotics in depression: connecting dots of gut-brain-axis through hypothalamic-pituitary adrenal axis and tryptophan\/kynurenic pathway involving indoleamine-2,3-dioxygenase.","volume":"62","author":"Tiwari","year":"2025","journal-title":"Mol. Neurobiol"},{"key":"B70","doi-asserted-by":"publisher","first-page":"100270","DOI":"10.1016\/j.ensci.2020.100270","article-title":"Kynurenine pathway in Parkinson\u2019s disease-An update.","volume":"21","author":"Venkatesan","year":"2020","journal-title":"eNeurologicalSci"},{"key":"B71","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s11064-025-04613-6","article-title":"Progress and perspectives on the estrogen-microbiota-brain axis in Alzheimer\u2019s Disease.","volume":"51","author":"Wang","year":"2025","journal-title":"Neurochem. Res"},{"key":"B72","doi-asserted-by":"publisher","first-page":"fcaa110","DOI":"10.1093\/braincomms\/fcaa110","article-title":"Gut dysbiosis in Huntington\u2019s disease: associations among gut microbiota, cognitive performance and clinical outcomes.","volume":"2","author":"Wasser","year":"2020","journal-title":"Brain Commun"},{"key":"B73","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/j.ejmech.2017.11.088","article-title":"Recent discovery of indoleamine-2,3-dioxygenase 1 inhibitors targeting cancer immunotherapy.","volume":"143","author":"Weng","year":"2018","journal-title":"Eur. J. Med. Chem"},{"key":"B74","doi-asserted-by":"publisher","first-page":"3769","DOI":"10.1007\/s00018-017-2550-9","article-title":"Microbiome, probiotics and neurodegenerative diseases: deciphering the gut brain axis.","volume":"74","author":"Westfall","year":"2017","journal-title":"Cell Mol. Life Sci"},{"key":"B75","doi-asserted-by":"publisher","first-page":"228","DOI":"10.3390\/nu13010228","article-title":"Altered gut microbial metabolites in amnestic mild cognitive impairment and Alzheimer\u2019s Disease: signals in host-microbe interplay.","volume":"13","author":"Wu","year":"2021","journal-title":"Nutrients"},{"key":"B76","doi-asserted-by":"publisher","first-page":"119491","DOI":"10.1016\/j.biomaterials.2019.119491","article-title":"Nanomaterial-based blood-brain-barrier (BBB) crossing strategies.","volume":"224","author":"Xie","year":"2019","journal-title":"Biomaterials"},{"key":"B77","doi-asserted-by":"publisher","first-page":"2168","DOI":"10.14336\/AD.2024.0134","article-title":"Tryptophan metabolism in Alzheimer\u2019s disease with the involvement of microglia and astrocyte crosstalk and gut-brain axis.","volume":"15","author":"Xie","year":"2024","journal-title":"Aging Dis"},{"key":"B78","doi-asserted-by":"publisher","first-page":"114081","DOI":"10.1016\/j.expneurol.2022.114081","article-title":"Indole-3-propionic acid alleviates ischemic brain injury in a mouse middle cerebral artery occlusion model.","volume":"353","author":"Xie","year":"2022","journal-title":"Exp. Neurol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"e22035","DOI":"10.1097\/MD.0000000000022035","article-title":"Fecal microbiota transplantation therapy for Parkinson\u2019s disease: a preliminary study.","volume":"99","author":"Xue","year":"2020","journal-title":"Medicine"},{"key":"B80","doi-asserted-by":"publisher","first-page":"1406856","DOI":"10.3389\/fcvm.2024.1406856","article-title":"The role of the kynurenine pathway in cardiovascular disease.","volume":"11","author":"Yang","year":"2024","journal-title":"Front. Cardiovasc. Med"},{"key":"B81","doi-asserted-by":"publisher","first-page":"903526","DOI":"10.3389\/fimmu.2022.903526","article-title":"Dual role of indoles derived from intestinal microbiota on human health.","volume":"13","author":"Ye","year":"2022","journal-title":"Front. Immunol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"4732","DOI":"10.1021\/acs.jafc.1c00706","article-title":"Ameliorative effect of dietary tryptophan on neurodegeneration and inflammation in d-galactose-induced aging mice with the potential mechanism relying on AMPK\/SIRT1\/PGC-1\u03b1 pathway and gut microbiota.","volume":"69","author":"Yin","year":"2021","journal-title":"J. Agric. Food Chem"},{"key":"B83","doi-asserted-by":"publisher","first-page":"1371791","DOI":"10.3389\/fneur.2024.1371791","article-title":"Effect of BF 839 + earthworm protein supplement on motor and some non-motor symptoms of Parkinson\u2019s disease: a randomized clinical trial.","volume":"15","author":"Zeng","year":"2024","journal-title":"Front. Neurol"},{"key":"B84","doi-asserted-by":"publisher","first-page":"2180","DOI":"10.1038\/s41593-025-02049-3","article-title":"TDP-43 nuclear loss in FTD\/ALS causes widespread alternative polyadenylation changes.","volume":"28","author":"Zeng","year":"2025","journal-title":"Nat. Neurosci"},{"key":"B85","doi-asserted-by":"publisher","first-page":"4272","DOI":"10.1038\/s41467-018-06675-3","article-title":"Modulation of AMPA receptor surface diffusion restores hippocampal plasticity and memory in Huntington\u2019s disease models.","volume":"9","author":"Zhang","year":"2018","journal-title":"Nat. Commun"},{"key":"B86","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s13073-016-0296-x","article-title":"Microbial metabolism of dietary components to bioactive metabolites: opportunities for new therapeutic interventions.","volume":"8","author":"Zhang","year":"2016","journal-title":"Genome Med"},{"key":"B87","doi-asserted-by":"publisher","first-page":"1646740","DOI":"10.3389\/fimmu.2025.1646740","article-title":"Bidirectional crosstalk between microglia and serotonin signaling in neuroinflammation and CNS disorders.","volume":"16","author":"Zheng","year":"2025","journal-title":"Front. Immunol"},{"key":"B88","doi-asserted-by":"publisher","first-page":"109690","DOI":"10.1016\/j.neuropharm.2023.109690","article-title":"The role of the indoles in microbiota-gut-brain axis and potential therapeutic targets: a focus on human neurological and neuropsychiatric diseases.","volume":"239","author":"Zhou","year":"2023","journal-title":"Neuropharmacology"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1820111\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:47:51Z","timestamp":1779256071000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1820111\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":88,"alternative-id":["10.3389\/fmicb.2026.1820111"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1820111","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]},"article-number":"1820111"}}