{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:54:52Z","timestamp":1789541692440,"version":"build-2803163510"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":37,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the Science and Technology Project of Beijing Life Science Academy","award":["2023100CC0190"],"award-info":[{"award-number":["2023100CC0190"]}]},{"name":"the Science and Technology Project of Beijing Life Science Academy","award":["2024100CC0090"],"award-info":[{"award-number":["2024100CC0090"]}]},{"name":"the Science and Technology Project of Beijing Life Science Academy","award":["2024100CC0100"],"award-info":[{"award-number":["2024100CC0100"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biol Sex Differ"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Parkinson\u2019s disease (PD) is a neurodegenerative disorder with established sex differences in incidence and progression. Epidemiological evidence suggests nicotine may confer protection against PD, but its mechanisms, particularly regarding sex-specific effects, remain unclear. This study investigated the neuroprotective mechanisms of nicotine in a rotenone-induced PD rat model, with a specific focus on evaluating sex-dependent modulation across behavioral, pathological, and gut-related outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male and female Sprague-Dawley rats were administered rotenone (2\u00a0mg\/kg\/day, s.c.) for four weeks to induce PD. Nicotine (0.5\u00a0mg\/kg\/day, s.c.) was administered 30\u00a0min after rotenone. Motor function was assessed using rotarod and CatWalk XT gait analysis. Neuropathology in the substantia nigra was evaluated via immunofluorescence for \u03b1-synuclein and tyrosine hydroxylase (TH). Gut pathology was analyzed through colon histopathology (H&amp;E staining) and ELISA for IL-6 and \u03b1-synuclein. Gut microbiota composition was assessed by 16\u00a0S rDNA sequencing, and serum metabolomics was performed using UPLC-MS\/MS. Data were analyzed by two-way ANOVA with Tukey\u2019s post-hoc test.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nicotine significantly attenuated rotenone-induced motor impairments: males showed a superior response in balance-related parameters, while females exhibited enhanced efficacy in dynamic gait metrics. Pathologically, nicotine reduced nigral \u03b1-synuclein accumulation and TH depletion in both sexes, with males showing greater \u03b1-synuclein accumulation following rotenone exposure. Crucially, nicotine exclusively ameliorated colon histopathology, reduced plasma \u03b1-synuclein, and suppressed colon IL-6 in females, while attenuating intestinal \u03b1-synuclein accumulation in both sexes. Microbiota analysis revealed sex-divergent taxonomic shifts with nicotine treatment. Metabolomics showed significantly more extensive metabolic reprogramming in females, particularly affecting indole derivatives. Pearson correlations revealed significant sex-specific associations between altered serum indole derivatives and gut microbiota genera.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Nicotine exerts neuroprotection in PD through sex-dependent modulation of multiple pathological pathways, primarily involving the gut-microbiota-metabolite axis. Females benefit from enhanced gastrointestinal protection and metabolic reprogramming, while males show preferential motor balance restoration. These findings underscore the critical importance of sex-stratified therapeutic strategies for PD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13293-026-00865-1","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T11:14:43Z","timestamp":1772536483000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sex-specific metabolic and microbial remodeling in a rotenone-induced rat model of Parkinson\u2019s disease following nicotine administration"],"prefix":"10.1186","volume":"17","author":[{"given":"Zhen","family":"Ni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoge","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaqing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengpeng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyuan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"865_CR1","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1038\/ng.3043","volume":"46","author":"MA Nalls","year":"2014","unstructured":"Nalls MA, et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson\u2019s disease. Nat Genet. 2014;46:989\u201393.","journal-title":"Nat Genet"},{"key":"865_CR2","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","volume":"39","author":"W Dauer","year":"2003","unstructured":"Dauer W, Przedborski S. Parkinson\u2019s disease: mechanisms and models. Neuron. 2003;39:889\u2013909.","journal-title":"Neuron"},{"key":"865_CR3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.3654","author":"BS Connolly","year":"2014","unstructured":"Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease. JAMA. 2014;311(16):1670\u201383. https:\/\/doi.org\/10.1001\/jama.2014.3654.","journal-title":"JAMA"},{"key":"865_CR4","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.parkreldis.2018.08.011","volume":"58","author":"K Knudsen","year":"2019","unstructured":"Knudsen K, et al. Objective intestinal function in patients with idiopathic REM sleep behavior disorder. Parkinsonism Relat Disord. 2019;58:28\u201334.","journal-title":"Parkinsonism Relat Disord"},{"key":"865_CR5","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s40035-023-00392-8","volume":"12","author":"X Zhang","year":"2023","unstructured":"Zhang X, Tang B, Guo J. Parkinson\u2019s disease and gut microbiota: from clinical to mechanistic and therapeutic studies. Transl Neurodegener. 2023;12:59.","journal-title":"Transl Neurodegener"},{"key":"865_CR6","doi-asserted-by":"publisher","first-page":"2571","DOI":"10.1093\/brain\/awab156","volume":"144","author":"Q Wang","year":"2021","unstructured":"Wang Q, et al. The role of gut dysbiosis in Parkinson\u2019s disease: mechanistic insights and therapeutic options. Brain. 2021;144:2571\u201393.","journal-title":"Brain"},{"key":"865_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3233\/JAD-161141","volume":"58","author":"C Jiang","year":"2017","unstructured":"Jiang C, Li G, Huang P, Liu Z, Zhao B. The gut microbiota and Alzheimer\u2019s disease. J Alzheimers Dis. 2017;58:1\u201315.","journal-title":"J Alzheimers Dis"},{"key":"865_CR8","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1002\/mds.26942","volume":"32","author":"EM Hill-Burns","year":"2017","unstructured":"Hill-Burns EM, et al. Parkinson\u2019s disease and Parkinson\u2019s disease medications have distinct signatures of the gut microbiome. Mov Disord. 2017;32:739\u201349.","journal-title":"Mov Disord"},{"key":"865_CR9","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1038\/nrneurol.2015.197","volume":"11","author":"L Klingelhoefer","year":"2015","unstructured":"Klingelhoefer L, Reichmann H. Pathogenesis of Parkinson disease\u2013the gut-brain axis and environmental factors. Nat Rev Neurol. 2015;11:625\u201336.","journal-title":"Nat Rev Neurol"},{"key":"865_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-016-0002-0","volume":"3","author":"MC Houser","year":"2017","unstructured":"Houser MC, Tansey MG. The gut-brain axis: is intestinal inflammation a silent driver of Parkinson\u2019s disease pathogenesis? NPJ Parkinsons Dis. 2017;3:3.","journal-title":"NPJ Parkinsons Dis"},{"key":"865_CR11","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.neuron.2019.05.035","volume":"103","author":"S Kim","year":"2019","unstructured":"Kim S, et al. Transneuronal Propagation of Pathologic \u03b1-Synuclein from the Gut to the Brain Models Parkinson\u2019s Disease. Neuron. 2019;103:627\u2013e641627.","journal-title":"Neuron"},{"key":"865_CR12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25052915","author":"P Iwaniak","year":"2024","unstructured":"Iwaniak P, Owe-Larsson M, Urba\u0144ska EM. Microbiota, tryptophan and aryl hydrocarbon receptors as the target triad in Parkinson\u2019s disease\u2014a narrative review. Int J Mol Sci. 2024. https:\/\/doi.org\/10.3390\/ijms25052915.","journal-title":"Int J Mol Sci"},{"key":"865_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2024.1433747","author":"L Coretti","year":"2024","unstructured":"Coretti L, Buommino E, Lembo F. The aryl hydrocarbon receptor pathway: a linking bridge between the gut microbiome and neurodegenerative diseases. Front Cell Neurosci. 2024. https:\/\/doi.org\/10.3389\/fncel.2024.1433747.","journal-title":"Front Cell Neurosci"},{"key":"865_CR14","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.brainresbull.2021.08.013","volume":"176","author":"Y Zhou","year":"2021","unstructured":"Zhou Y, et al. Dynamic changes of activated AHR in microglia and astrocytes in the substantia nigra-striatum system in an MPTP-induced Parkinson\u2019s disease mouse model. Brain Res Bull. 2021;176:174\u201383.","journal-title":"Brain Res Bull"},{"key":"865_CR15","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1111\/nan.12298","volume":"42","author":"K Del Tredici","year":"2016","unstructured":"Del Tredici K, Braak H, Review. Sporadic Parkinson\u2019s disease: development and distribution of \u03b1-synuclein pathology. Neuropathol Appl Neurobiol. 2016;42:33\u201350.","journal-title":"Neuropathol Appl Neurobiol"},{"key":"865_CR16","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1016\/j.cell.2016.11.018","volume":"167","author":"TR Sampson","year":"2016","unstructured":"Sampson TR, et al. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson\u2019s Disease. Cell. 2016;167:1469\u2013e14801412.","journal-title":"Cell"},{"key":"865_CR17","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.673341","volume":"12","author":"X Gui","year":"2021","unstructured":"Gui X, Yang Z, Li MD. Effect of cigarette smoke on gut microbiota: state of knowledge. Front Physiol. 2021;12:673341.","journal-title":"Front Physiol"},{"key":"865_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-025-00761-0","author":"E Parrella","year":"2025","unstructured":"Parrella E, et al. Sex-related differences in phenotype and nigro-striatal degeneration of c-rel-\/- mouse model of Parkinson\u2019s disease. Biol Sex Differ. 2025. https:\/\/doi.org\/10.1186\/s13293-025-00761-0.","journal-title":"Biol Sex Differ"},{"key":"865_CR19","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.parkreldis.2019.12.006","volume":"71","author":"R Kim","year":"2020","unstructured":"Kim R, Yoo D, Jung YJ, Han K, Lee JY. Sex differences in smoking, alcohol consumption, and risk of Parkinson\u2019s disease: a nationwide cohort study. Parkinsonism Relat Disord. 2020;71:60\u20135.","journal-title":"Parkinsonism Relat Disord"},{"key":"865_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2021.173862","volume":"895","author":"B Vaidya","year":"2021","unstructured":"Vaidya B, Dhamija K, Guru P, Sharma SS. Parkinson\u2019s disease in women: mechanisms underlying sex differences. Eur J Pharmacol. 2021;895:173862.","journal-title":"Eur J Pharmacol"},{"key":"865_CR21","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1111\/j.1468-1331.2007.01949.x","volume":"14","author":"G Villafane","year":"2007","unstructured":"Villafane G, et al. Chronic high dose transdermal nicotine in Parkinson\u2019s disease: an open trial. Eur J Neurol. 2007;14:1313\u20136.","journal-title":"Eur J Neurol"},{"key":"865_CR22","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1111\/j.1460-9568.2007.05636.x","volume":"26","author":"HJ Park","year":"2007","unstructured":"Park HJ, et al. Neuroprotective effect of nicotine on dopaminergic neurons by anti-inflammatory action. Eur J Neurosci. 2007;26:79\u201389.","journal-title":"Eur J Neurosci"},{"key":"865_CR23","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-025-05342-1","author":"Z Ni","year":"2025","unstructured":"Ni Z, et al. Nicotine improves memory impairment in aged rats through enhanced mitochondrial homeostasis. Mol Neurobiol. 2025. https:\/\/doi.org\/10.1007\/s12035-025-05342-1.","journal-title":"Mol Neurobiol"},{"key":"865_CR24","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.1021\/acs.chemrestox.7b00162","volume":"30","author":"L Chi","year":"2017","unstructured":"Chi L, et al. Nicotine alters the gut microbiome and metabolites of gut-brain interactions in a sex-specific manner. Chem Res Toxicol. 2017;30:2110\u20139.","journal-title":"Chem Res Toxicol"},{"key":"865_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-06256-9","author":"P Fang","year":"2024","unstructured":"Fang P, et al. Sex-dependent interactions between prodromal intestinal inflammation and LRRK2 G2019S in mice promote endophenotypes of Parkinson\u2019s disease. Commun Biol. 2024. https:\/\/doi.org\/10.1038\/s42003-024-06256-9.","journal-title":"Commun Biol"},{"key":"865_CR26","doi-asserted-by":"publisher","first-page":"2549","DOI":"10.1007\/s11095-013-1005-8","volume":"30","author":"R Huang","year":"2013","unstructured":"Huang R, et al. Angiopep-conjugated nanoparticles for targeted long-term gene therapy of Parkinson\u2019s disease. Pharm Res. 2013;30:2549\u201359.","journal-title":"Pharm Res"},{"key":"865_CR27","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.brainres.2016.11.020","volume":"1655","author":"ZN Zhang","year":"2017","unstructured":"Zhang ZN, et al. Subcutaneous rotenone rat model of Parkinson\u2019s disease: dose exploration study. Brain Res. 2017;1655:104\u201313.","journal-title":"Brain Res"},{"key":"865_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2020.135360","volume":"738","author":"C Sun","year":"2020","unstructured":"Sun C, Jia G, Wang X, Wang Y, Liu Y. Immunoproteasome is up-regulated in rotenone-induced Parkinson\u2019s disease rat model. Neurosci Lett. 2020;738:135360.","journal-title":"Neurosci Lett"},{"key":"865_CR29","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1038\/nmeth.2604","volume":"10","author":"RC Edgar","year":"2013","unstructured":"Edgar RC. UPARSE: highly accurate OTU sequences from microbial amplicon reads. Nat Methods. 2013;10:996\u20138.","journal-title":"Nat Methods"},{"key":"865_CR30","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-021-01107-9","author":"Z Zhao","year":"2021","unstructured":"Zhao Z, et al. Fecal microbiota transplantation protects rotenone-induced Parkinson\u2019s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis. Microbiome. 2021. https:\/\/doi.org\/10.1186\/s40168-021-01107-9.","journal-title":"Microbiome"},{"key":"865_CR31","doi-asserted-by":"publisher","first-page":"5261","DOI":"10.1128\/AEM.00062-07","volume":"73","author":"Q Wang","year":"2007","unstructured":"Wang Q, Garrity GM, Tiedje JM, Cole JR. Na\u00efve bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol. 2007;73:5261\u20137.","journal-title":"Appl Environ Microbiol"},{"key":"865_CR32","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nmeth.f.303","volume":"7","author":"JG Caporaso","year":"2010","unstructured":"Caporaso JG, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7:335\u20136.","journal-title":"Nat Methods"},{"key":"865_CR33","doi-asserted-by":"publisher","DOI":"10.1093\/toxres\/tfae002","volume":"13","author":"Y Tian","year":"2024","unstructured":"Tian Y, et al. Liver toxicity in rats after subchronic exposure to HTP aerosol and cigarette smoke. Toxicol Res (Camb). 2024;13:tfae002.","journal-title":"Toxicol Res (Camb)"},{"key":"865_CR34","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1038\/s41582-019-0294-x","volume":"16","author":"S Meoni","year":"2020","unstructured":"Meoni S, Macerollo A, Moro E. Sex differences in movement disorders. Nat Rev Neurol. 2020;16:84\u201396.","journal-title":"Nat Rev Neurol"},{"key":"865_CR35","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1111\/ene.15801","volume":"30","author":"R Bovenzi","year":"2023","unstructured":"Bovenzi R, et al. Sex hormones differentially contribute to Parkinson disease in males: a multimodal biomarker study. Eur J Neurol. 2023;30:1983\u201390.","journal-title":"Eur J Neurol"},{"key":"865_CR36","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1210\/endrev\/bnz005","volume":"41","author":"E Vegeto","year":"2020","unstructured":"Vegeto E, et al. The role of sex and sex hormones in neurodegenerative diseases. Endocr Rev. 2020;41:273\u2013319.","journal-title":"Endocr Rev"},{"key":"865_CR37","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.834580","author":"S Lerche","year":"2022","unstructured":"Lerche S, et al. CSF and serum levels of inflammatory markers in PD: sparse correlation, sex differences and association with neurodegenerative biomarkers. Front Neurol. 2022. https:\/\/doi.org\/10.3389\/fneur.2022.834580.","journal-title":"Front Neurol"},{"key":"865_CR38","doi-asserted-by":"crossref","unstructured":"Joers V et al. Microglia, inflammation and gut microbiota responses in a progressive monkey model of Parkinson\u2019s disease: A case series. Neurobiol Dis 144 (2020).","DOI":"10.1016\/j.nbd.2020.105027"},{"key":"865_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115554","author":"W Dong","year":"2023","unstructured":"Dong W, et al. Estrogen plays an important role by influencing the NLRP3 inflammasome. Biomed Pharmacother. 2023. https:\/\/doi.org\/10.1016\/j.biopha.2023.115554.","journal-title":"Biomed Pharmacother"},{"key":"865_CR40","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2023.110668","author":"M Bourque","year":"2023","unstructured":"Bourque M, Morissette M, Soulet D, Di Paolo T. Impact of sex on neuroimmune contributions to Parkinson\u2019s disease. Brain Res Bull. 2023. https:\/\/doi.org\/10.1016\/j.brainresbull.2023.110668.","journal-title":"Brain Res Bull"},{"key":"865_CR41","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2019.100788","author":"C Yilmaz","year":"2019","unstructured":"Yilmaz C, et al. Neurosteroids as regulators of neuroinflammation. Front Neuroendocrinol. 2019. https:\/\/doi.org\/10.1016\/j.yfrne.2019.100788.","journal-title":"Front Neuroendocrinol"},{"key":"865_CR42","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1111\/cns.13990","volume":"29","author":"Z Li","year":"2022","unstructured":"Li Z, et al. Gut bacterial profiles in Parkinson\u2019s disease: A systematic review. CNS Neurosci Ther. 2022;29:140\u201357.","journal-title":"CNS Neurosci Ther"},{"key":"865_CR43","doi-asserted-by":"publisher","first-page":"6737","DOI":"10.1007\/s00253-023-12789-6","volume":"107","author":"S Nie","year":"2023","unstructured":"Nie S, Ge Y. The link between the gut microbiome, inflammation, and Parkinson\u2019s disease. Appl Microbiol Biotechnol. 2023;107:6737\u201349.","journal-title":"Appl Microbiol Biotechnol"},{"key":"865_CR44","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.bbi.2024.01.010","volume":"117","author":"J Liu","year":"2024","unstructured":"Liu J, et al. Microbiota-microglia crosstalk between Blautia producta and neuroinflammation of Parkinson\u2019s disease: a bench-to-bedside translational approach. Brain Behav Immun. 2024;117:270\u201382.","journal-title":"Brain Behav Immun"},{"key":"865_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-025-00885-5","author":"JR Bedarf","year":"2025","unstructured":"Bedarf JR, et al. A prebiotic dietary pilot intervention restores faecal metabolites and may be neuroprotective in Parkinson\u2019s Disease. NPJ Parkinsons Dis. 2025. https:\/\/doi.org\/10.1038\/s41531-025-00885-5.","journal-title":"NPJ Parkinsons Dis"},{"key":"865_CR46","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01549-0","author":"W Zhang","year":"2023","unstructured":"Zhang W, et al. Neuroprotective effect of a medium-chain triglyceride ketogenic diet on MPTP-induced Parkinson\u2019s disease mice: a combination of transcriptomics and metabolomics in the substantia nigra and fecal microbiome. Cell Death Discov. 2023. https:\/\/doi.org\/10.1038\/s41420-023-01549-0.","journal-title":"Cell Death Discov"},{"key":"865_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2025.115766","author":"X Zuo","year":"2025","unstructured":"Zuo X, Zhang T, Dong X, Liu J, Liu Y. Identification of the key tryptophan metabolic characteristics of Lactiplantibacillus plantarum for aryl hydrocarbon receptor activation and ulcerative colitis alleviation. Food Res Int. 2025. https:\/\/doi.org\/10.1016\/j.foodres.2025.115766.","journal-title":"Food Res Int"},{"key":"865_CR48","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70406","author":"C Yang","year":"2025","unstructured":"Yang C, et al. Synbiotics of Lactobacillus suilingensis and inulin alleviates cognitive impairment via regulating gut microbiota indole-3\u2010lactic acid metabolism in female AD mice. Alzheimer\u2019s & Dementia. 2025. https:\/\/doi.org\/10.1002\/alz.70406.","journal-title":"Alzheimer's & Dementia"},{"key":"865_CR49","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2025.2467235","author":"H Gao","year":"2025","unstructured":"Gao H, et al. Microbiota-derived IPA alleviates intestinal mucosal inflammation through upregulating Th1\/Th17 cell apoptosis in inflammatory bowel disease. Gut Microbes. 2025. https:\/\/doi.org\/10.1080\/19490976.2025.2467235.","journal-title":"Gut Microbes"},{"key":"865_CR50","doi-asserted-by":"publisher","first-page":"5208","DOI":"10.1021\/acs.jafc.4c08548","volume":"73","author":"Z Hao","year":"2025","unstructured":"Hao Z, et al. Indole-3-propionic acid attenuates neuroinflammation and cognitive deficits by inhibiting the RAGE-JAK2-STAT3 signaling pathway. J Agric Food Chem. 2025;73:5208\u201322.","journal-title":"J Agric Food Chem"},{"key":"865_CR51","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.cmet.2020.03.003","volume":"31","author":"EC Rosser","year":"2020","unstructured":"Rosser EC, et al. Microbiota-Derived Metabolites Suppress Arthritis by Amplifying Aryl-Hydrocarbon Receptor Activation in Regulatory B Cells. Cell Metab. 2020;31:837\u2013e851810.","journal-title":"Cell Metab"},{"key":"865_CR52","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/j.cell.2022.01.010","volume":"185","author":"M De Giovanni","year":"2022","unstructured":"De Giovanni M, et al. GPR35 promotes neutrophil recruitment in response to serotonin metabolite 5-HIAA. Cell. 2022;185:815\u2013e830819.","journal-title":"Cell"},{"key":"865_CR53","doi-asserted-by":"crossref","unstructured":"He Y et al. Disturbances of the gut microbiota-derived tryptophan metabolites as key actors in vagotomy-induced mastitis in mice. Cell Rep 44 (2024).","DOI":"10.1016\/j.celrep.2024.114585"}],"container-title":["Biology of Sex Differences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13293-026-00865-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13293-026-00865-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13293-026-00865-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T13:09:24Z","timestamp":1775740164000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13293-026-00865-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,3]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["865"],"URL":"https:\/\/doi.org\/10.1186\/s13293-026-00865-1","relation":{},"ISSN":["2042-6410"],"issn-type":[{"value":"2042-6410","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,3]]},"assertion":[{"value":"10 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal treatment procedures adhered to the guidelines of the Laboratory Animal Management and Ethics Committee of the China Tobacco Quality Supervision and Test Center (protocol code: CTQTC-SYXK-2023015).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"74"}}