{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:18:25Z","timestamp":1792498705424,"version":"4.5.0"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":46,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100020206","name":"Korea Dementia Research Center","doi-asserted-by":"publisher","award":["RS-2022-KH128705"],"award-info":[{"award-number":["RS-2022-KH128705"]}],"id":[{"id":"10.13039\/100020206","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020206","name":"Korea Dementia Research Center","doi-asserted-by":"publisher","award":["RS-2020-KH106747"],"award-info":[{"award-number":["RS-2020-KH106747"]}],"id":[{"id":"10.13039\/100020206","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2023-00273634"],"award-info":[{"award-number":["RS-2023-00273634"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"DOI":"10.1186\/s12974-026-03796-1","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:35:14Z","timestamp":1776990914000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tryptophan\u2013kynurenine metabolic reprogramming along the gut\u2013brain axis alleviates Alzheimer\u2019s pathology"],"prefix":"10.1186","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6518-4750","authenticated-orcid":false,"given":"Hyunjung","family":"Choi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7669-2732","authenticated-orcid":false,"given":"Seok Beom","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunchae","family":"Joung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukyung","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiah","family":"Cha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Yong","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Sang","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayoung","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Won","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Hwan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang Hun","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do Yup","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7085-4085","authenticated-orcid":false,"given":"Inhee","family":"Mook-Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"issue":"10","key":"3796_CR1","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1038\/nm.4185","volume":"22","author":"BO Schroeder","year":"2016","unstructured":"Schroeder BO, Backhed F. Signals from the gut microbiota to distant organs in physiology and disease. Nat Med. 2016;22(10):1079\u201389.","journal-title":"Nat Med"},{"issue":"1","key":"3796_CR2","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41392-022-00974-4","volume":"7","author":"K Hou","year":"2022","unstructured":"Hou K, Wu ZX, Chen XY, Wang JQ, Zhang D, Xiao C, et al. Microbiota in health and diseases. Signal Transduct Target Ther. 2022;7(1):135.","journal-title":"Signal Transduct Target Ther"},{"issue":"7898","key":"3796_CR3","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/s41586-022-04396-8","volume":"602","author":"BD Needham","year":"2022","unstructured":"Needham BD, Funabashi M, Adame MD, Wang Z, Boktor JC, Haney J, et al. A gut-derived metabolite alters brain activity and anxiety behaviour in mice. Nature. 2022;602(7898):647\u201353.","journal-title":"Nature"},{"issue":"2","key":"3796_CR4","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1038\/nn.4476","volume":"20","author":"TC Fung","year":"2017","unstructured":"Fung TC, Olson CA, Hsiao EY. Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci. 2017;20(2):145\u201355.","journal-title":"Nat Neurosci"},{"issue":"7","key":"3796_CR5","doi-asserted-by":"publisher","first-page":"3002","DOI":"10.1038\/s41380-023-02071-6","volume":"28","author":"E Siopi","year":"2023","unstructured":"Siopi E, Galerne M, Rivagorda M, Saha S, Moigneu C, Moriceau S, et al. Gut microbiota changes require vagus nerve integrity to promote depressive-like behaviors in mice. Mol Psychiatry. 2023;28(7):3002\u201312.","journal-title":"Mol Psychiatry"},{"issue":"1","key":"3796_CR6","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1038\/s41398-021-01443-2","volume":"11","author":"Y Guo","year":"2021","unstructured":"Guo Y, Zhu X, Zeng M, Qi L, Tang X, Wang D, et al. A diet high in sugar and fat influences neurotransmitter metabolism and then affects brain function by altering the gut microbiota. Transl Psychiatry. 2021;11(1):328.","journal-title":"Transl Psychiatry"},{"key":"3796_CR7","doi-asserted-by":"publisher","first-page":"104527","DOI":"10.1016\/j.ebiom.2023.104527","volume":"90","author":"L Liu","year":"2023","unstructured":"Liu L, Wang H, Chen X, Zhang Y, Zhang H, Xie P. Gut microbiota and its metabolites in depression: from pathogenesis to treatment. EBioMedicine. 2023;90:104527.","journal-title":"EBioMedicine"},{"key":"3796_CR8","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.bbi.2024.04.002","volume":"119","author":"Q Xu","year":"2024","unstructured":"Xu Q, Sun L, Chen Q, Jiao C, Wang Y, Li H, et al. Gut microbiota dysbiosis contributes to depression-like behaviors via hippocampal NLRP3-mediated neuroinflammation in a postpartum depression mouse model. Brain Behav Immun. 2024;119:220\u201335.","journal-title":"Brain Behav Immun"},{"issue":"1","key":"3796_CR9","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/s41398-023-02325-5","volume":"13","author":"MI Butler","year":"2023","unstructured":"Butler MI, Bastiaanssen TFS, Long-Smith C, Morkl S, Berding K, Ritz NL, et al. The gut microbiome in social anxiety disorder: evidence of altered composition and function. Transl Psychiatry. 2023;13(1):95.","journal-title":"Transl Psychiatry"},{"issue":"3","key":"3796_CR10","doi-asserted-by":"publisher","first-page":"101982","DOI":"10.1016\/j.xcrm.2025.101982","volume":"6","author":"KJ O'Riordan","year":"2025","unstructured":"O\u2019Riordan KJ, Moloney GM, Keane L, Clarke G, Cryan JF. The gut microbiota-immune-brain axis: therapeutic implications. Cell Rep Med. 2025;6(3):101982.","journal-title":"Cell Rep Med"},{"key":"3796_CR11","doi-asserted-by":"publisher","first-page":"101802","DOI":"10.1016\/j.smim.2023.101802","volume":"69","author":"S Carloni","year":"2023","unstructured":"Carloni S, Rescigno M. The gut-brain vascular axis in neuroinflammation. Semin Immunol. 2023;69:101802.","journal-title":"Semin Immunol"},{"issue":"1","key":"3796_CR12","doi-asserted-by":"publisher","first-page":"2167172","DOI":"10.1080\/19490976.2023.2167172","volume":"15","author":"J Jin","year":"2023","unstructured":"Jin J, Xu Z, Zhang L, Zhang C, Zhao X, Mao Y, et al. Gut-derived beta-amyloid: Likely a centerpiece of the gut-brain axis contributing to Alzheimer\u2019s pathogenesis. Gut Microbes. 2023;15(1):2167172.","journal-title":"Gut Microbes"},{"issue":"2","key":"3796_CR13","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1136\/gutjnl-2018-317431","volume":"69","author":"MS Kim","year":"2020","unstructured":"Kim MS, Kim Y, Choi H, Kim W, Park S, Lee D, et al. Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer\u2019s disease animal model. Gut. 2020;69(2):283\u201394.","journal-title":"Gut"},{"issue":"4","key":"3796_CR14","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.3233\/JAD-215235","volume":"86","author":"H Choi","year":"2022","unstructured":"Choi H, Lee D, Mook-Jung I. Gut Microbiota as a Hidden Player in the Pathogenesis of Alzheimer\u2019s Disease. J Alzheimers Dis. 2022;86(4):1501\u201326.","journal-title":"J Alzheimers Dis"},{"key":"3796_CR15","doi-asserted-by":"publisher","first-page":"102730","DOI":"10.1016\/j.conb.2023.102730","volume":"81","author":"H Choi","year":"2023","unstructured":"Choi H, Mook-Jung I. Functional effects of gut microbiota-derived metabolites in Alzheimer\u2019s disease. Curr Opin Neurobiol. 2023;81:102730.","journal-title":"Curr Opin Neurobiol"},{"key":"3796_CR16","doi-asserted-by":"publisher","first-page":"114778","DOI":"10.1016\/j.physbeh.2024.114778","volume":"290","author":"JN Manfredi","year":"2025","unstructured":"Manfredi JN, Gupta SK, Vyavahare S, Deak F, Lu X, Buddha L, et al. Gut microbiota dysbiosis in Alzheimer\u2019s disease (AD): Insights from human clinical studies and the mouse AD models. Physiol Behav. 2025;290:114778.","journal-title":"Physiol Behav"},{"key":"3796_CR17","doi-asserted-by":"publisher","first-page":"41802","DOI":"10.1038\/srep41802","volume":"7","author":"T Harach","year":"2017","unstructured":"Harach T, Marungruang N, Duthilleul N, Cheatham V, Mc Coy KD, Frisoni G, et al. Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota. Sci Rep. 2017;7:41802.","journal-title":"Sci Rep"},{"issue":"7","key":"3796_CR18","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1084\/jem.20182386","volume":"216","author":"HB Dodiya","year":"2019","unstructured":"Dodiya HB, Kuntz T, Shaik SM, Baufeld C, Leibowitz J, Zhang X, et al. Sex-specific effects of microbiome perturbations on cerebral Abeta amyloidosis and microglia phenotypes. J Exp Med. 2019;216(7):1542\u201360.","journal-title":"J Exp Med"},{"issue":"11","key":"3796_CR19","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1136\/gutjnl-2021-326269","volume":"71","author":"C Chen","year":"2022","unstructured":"Chen C, Liao J, Xia Y, Liu X, Jones R, Haran J, et al. Gut microbiota regulate Alzheimer\u2019s disease pathologies and cognitive disorders via PUFA-associated neuroinflammation. Gut. 2022;71(11):2233\u201352.","journal-title":"Gut"},{"issue":"5","key":"3796_CR20","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1038\/s41591-019-0439-x","volume":"25","author":"J Suez","year":"2019","unstructured":"Suez J, Zmora N, Segal E, Elinav E. The pros, cons, and many unknowns of probiotics. Nat Med. 2019;25(5):716\u201329.","journal-title":"Nat Med"},{"issue":"10","key":"3796_CR21","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/s41575-019-0173-3","volume":"16","author":"ME Sanders","year":"2019","unstructured":"Sanders ME, Merenstein DJ, Reid G, Gibson GR, Rastall RA. Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nat Rev Gastroenterol Hepatol. 2019;16(10):605\u201316.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"2","key":"3796_CR22","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1007\/s12602-019-09577-y","volume":"12","author":"CS Lee","year":"2020","unstructured":"Lee CS, Kim SH. Anti-inflammatory and anti-osteoporotic potential of Lactobacillus plantarum A41 and L. fermentum SRK414 as probiotics. Probiotics Antimicrob Proteins. 2020;12(2):623\u201334.","journal-title":"Probiotics Antimicrob Proteins"},{"issue":"1","key":"3796_CR23","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-017-0234-4","volume":"13","author":"DK Kim","year":"2018","unstructured":"Kim DK, Park J, Han D, Yang J, Kim A, Woo J, et al. Molecular and functional signatures in a novel Alzheimer\u2019s disease mouse model assessed by quantitative proteomics. Mol Neurodegener. 2018;13(1):2.","journal-title":"Mol Neurodegener"},{"key":"3796_CR24","doi-asserted-by":"publisher","DOI":"10.3390\/nu16244260","author":"H Jang","year":"2024","unstructured":"Jang H, Joung H, Chu J, Cho M, Kim YW, Kim KH, et al. Lactobacillus delbrueckii subsp. lactis CKDB001 ameliorates metabolic complications in high-fat diet-induced obese mice. Nutrients. 2024. https:\/\/doi.org\/10.3390\/nu16244260.","journal-title":"Nutrients"},{"key":"3796_CR25","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/978-1-4939-8994-2_10","volume":"1916","author":"AK Kraeuter","year":"2019","unstructured":"Kraeuter AK, Guest PC, Sarnyai Z. The Y-Maze for Assessment of Spatial Working and Reference Memory in Mice. Methods Mol Biol. 2019;1916:105\u201311.","journal-title":"Methods Mol Biol"},{"issue":"3","key":"3796_CR26","doi-asserted-by":"publisher","first-page":"e3162","DOI":"10.21769\/BioProtoc.3162","volume":"9","author":"EAK Prieur","year":"2019","unstructured":"Prieur EAK, Jadavji NM. Assessing spatial working memory using the spontaneous alternation Y-maze test in aged male mice. Bio-Protoc. 2019;9(3):e3162.","journal-title":"Bio-Protoc"},{"key":"3796_CR27","doi-asserted-by":"crossref","unstructured":"Lueptow LM. Novel object recognition test for the investigation of learning and memory in mice. J Vis Exp. 2017(126).","DOI":"10.3791\/55718-v"},{"key":"3796_CR28","doi-asserted-by":"publisher","first-page":"1512217","DOI":"10.3389\/fmicb.2024.1512217","volume":"15","author":"DB Lee","year":"2024","unstructured":"Lee DB, Hwang IS. Macronutrient balance determines the human gut microbiome eubiosis: insights from in vitro gastrointestinal digestion and fermentation of eight pulse species. Front Microbiol. 2024;15:1512217.","journal-title":"Front Microbiol"},{"issue":"Database issue","key":"3796_CR29","first-page":"D590","volume":"41","author":"C Quast","year":"2013","unstructured":"Quast C, Pruesse E, Yilmaz P, Gerken J, Schweer T, Yarza P, et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res. 2013;41(Database issue):D590-6.","journal-title":"Nucleic Acids Res"},{"issue":"8","key":"3796_CR30","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","volume":"37","author":"E Bolyen","year":"2019","unstructured":"Bolyen E, Rideout JR, Dillon MR, Bokulich NA, Abnet CC, Al-Ghalith GA, et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol. 2019;37(8):852\u20137.","journal-title":"Nat Biotechnol"},{"issue":"7541","key":"3796_CR31","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/nature14232","volume":"519","author":"B Chassaing","year":"2015","unstructured":"Chassaing B, Koren O, Goodrich JK, Poole AC, Srinivasan S, Ley RE, et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. 2015;519(7541):92\u20136.","journal-title":"Nature"},{"issue":"2","key":"3796_CR32","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1136\/gutjnl-2024-334571","volume":"75","author":"H Choi","year":"2026","unstructured":"Choi H, Hong SB, Liu HW, Song H, Jeong JH, Ahn K, et al. Pathological tau propagation from the brain to the colon via the vagal efferent pathway in Alzheimer\u2019s disease. Gut. 2026;75(2):302\u201315.","journal-title":"Gut"},{"issue":"7","key":"3796_CR33","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1038\/nbt.1883","volume":"29","author":"MG Grabherr","year":"2011","unstructured":"Grabherr MG, Haas BJ, Yassour M, Levin JZ, Thompson DA, Amit I, et al. Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nat Biotechnol. 2011;29(7):644\u201352.","journal-title":"Nat Biotechnol"},{"issue":"12","key":"3796_CR34","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550.","journal-title":"Genome Biol"},{"issue":"43","key":"3796_CR35","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102(43):15545\u201350.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"3796_CR36","doi-asserted-by":"publisher","first-page":"845","DOI":"10.3350\/cmh.2024.0349","volume":"30","author":"SP Sharma","year":"2024","unstructured":"Sharma SP, Gupta H, Kwon GH, Lee SY, Song SH, Kim JS, et al. Gut microbiome and metabolome signatures in liver cirrhosis-related complications. Clin Mol Hepatol. 2024;30(4):845\u201362.","journal-title":"Clin Mol Hepatol"},{"issue":"5","key":"3796_CR37","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/j.neuron.2013.05.029","volume":"78","author":"Y Zhang","year":"2013","unstructured":"Zhang Y, Pak C, Han Y, Ahlenius H, Zhang Z, Chanda S, et al. Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron. 2013;78(5):785\u201398.","journal-title":"Neuron"},{"key":"3796_CR38","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.ymeth.2015.11.019","volume":"101","author":"SM Ho","year":"2016","unstructured":"Ho SM, Hartley BJ, Tcw J, Beaumont M, Stafford K, Slesinger PA, et al. Rapid Ngn2-induction of excitatory neurons from hiPSC-derived neural progenitor cells. Methods. 2016;101:113\u201324.","journal-title":"Methods"},{"issue":"4","key":"3796_CR39","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1016\/j.stemcr.2017.08.019","volume":"9","author":"C Wang","year":"2017","unstructured":"Wang C, Ward ME, Chen R, Liu K, Tracy TE, Chen X, et al. Scalable Production of iPSC-Derived Human Neurons to Identify Tau-Lowering Compounds by High-Content Screening. Stem Cell Reports. 2017;9(4):1221\u201333.","journal-title":"Stem Cell Reports"},{"issue":"8","key":"3796_CR40","doi-asserted-by":"publisher","first-page":"2509","DOI":"10.1016\/j.celrep.2018.04.066","volume":"23","author":"R Nehme","year":"2018","unstructured":"Nehme R, Zuccaro E, Ghosh SD, Li C, Sherwood JL, Pietilainen O, et al. Combining NGN2 programming with developmental patterning generates human excitatory neurons with NMDAR-mediated synaptic transmission. Cell Rep. 2018;23(8):2509\u201323.","journal-title":"Cell Rep"},{"issue":"3","key":"3796_CR41","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.cmet.2019.06.005","volume":"30","author":"SH Baik","year":"2019","unstructured":"Baik SH, Kang S, Lee W, Choi H, Chung S, Kim JI, et al. A breakdown in metabolic reprogramming causes microglia dysfunction in Alzheimer\u2019s disease. Cell Metab. 2019;30(3):493-507 e6.","journal-title":"Cell Metab"},{"key":"3796_CR42","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/1471-2105-13-99","volume":"13","author":"DK Barupal","year":"2012","unstructured":"Barupal DK, Haldiya PK, Wohlgemuth G, Kind T, Kothari SL, Pinkerton KE, et al. MetaMapp: mapping and visualizing metabolomic data by integrating information from biochemical pathways and chemical and mass spectral similarity. BMC Bioinformatics. 2012;13:99.","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"3796_CR43","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s40478-018-0557-6","volume":"6","author":"J Neddens","year":"2018","unstructured":"Neddens J, Temmel M, Flunkert S, Kerschbaumer B, Hoeller C, Loeffler T, et al. Phosphorylation of different tau sites during progression of Alzheimer\u2019s disease. Acta Neuropathol Commun. 2018;6(1):52.","journal-title":"Acta Neuropathol Commun"},{"issue":"4","key":"3796_CR44","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1038\/ng859","volume":"30","author":"J Zhang","year":"2002","unstructured":"Zhang J, Zhang D, McQuade JS, Behbehani M, Tsien JZ, Xu M. c-fos regulates neuronal excitability and survival. Nat Genet. 2002;30(4):416\u201320.","journal-title":"Nat Genet"},{"key":"3796_CR45","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3389\/fendo.2016.00025","volume":"7","author":"L Torner","year":"2016","unstructured":"Torner L. Actions of prolactin in the brain: from physiological adaptations to stress and neurogenesis to psychopathology. Front Endocrinol (Lausanne). 2016;7:25.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"3796_CR46","first-page":"78","volume":"8","author":"K Minatohara","year":"2015","unstructured":"Minatohara K, Akiyoshi M, Okuno H. Role of immediate-early genes in synaptic plasticity and neuronal ensembles underlying the memory trace. Front Mol Neurosci. 2015;8:78.","journal-title":"Front Mol Neurosci"},{"issue":"3","key":"3796_CR47","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.neures.2010.12.007","volume":"69","author":"H Okuno","year":"2011","unstructured":"Okuno H. Regulation and function of immediate-early genes in the brain: beyond neuronal activity markers. Neurosci Res. 2011;69(3):175\u201386.","journal-title":"Neurosci Res"},{"issue":"1","key":"3796_CR48","doi-asserted-by":"publisher","first-page":"13765","DOI":"10.1038\/s41598-019-50228-7","volume":"9","author":"EA Cabrera-Reyes","year":"2019","unstructured":"Cabrera-Reyes EA, Vanoye-Carlo A, Rodriguez-Dorantes M, Vazquez-Martinez ER, Rivero-Segura NA, Collazo-Navarrete O, et al. Transcriptomic analysis reveals new hippocampal gene networks induced by prolactin. Sci Rep. 2019;9(1):13765.","journal-title":"Sci Rep"},{"issue":"6","key":"3796_CR49","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.1523\/JNEUROSCI.3178-08.2009","volume":"29","author":"L Torner","year":"2009","unstructured":"Torner L, Karg S, Blume A, Kandasamy M, Kuhn HG, Winkler J, et al. Prolactin prevents chronic stress-induced decrease of adult hippocampal neurogenesis and promotes neuronal fate. J Neurosci. 2009;29(6):1826\u201333.","journal-title":"J Neurosci"},{"issue":"1","key":"3796_CR50","doi-asserted-by":"publisher","first-page":"48","DOI":"10.5056\/jnm18087","volume":"25","author":"K Kowalski","year":"2019","unstructured":"Kowalski K, Mulak A. Brain-gut-microbiota axis in Alzheimer\u2019s disease. J Neurogastroenterol Motil. 2019;25(1):48\u201360.","journal-title":"J Neurogastroenterol Motil"},{"key":"3796_CR51","doi-asserted-by":"publisher","first-page":"925135","DOI":"10.1155\/2012\/925135","volume":"2012","author":"RV Luckheeram","year":"2012","unstructured":"Luckheeram RV, Zhou R, Verma AD, Xia B. CD4(+)T cells: differentiation and functions. Clin Dev Immunol. 2012;2012:925135.","journal-title":"Clin Dev Immunol"},{"issue":"1","key":"3796_CR52","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1186\/s12974-020-01873-7","volume":"17","author":"Y Wang","year":"2020","unstructured":"Wang Y, An Y, Ma W, Yu H, Lu Y, Zhang X, et al. 27-hydroxycholesterol contributes to cognitive deficits in APP\/PS1 transgenic mice through microbiota dysbiosis and intestinal barrier dysfunction. J Neuroinflammation. 2020;17(1):199.","journal-title":"J Neuroinflammation"},{"key":"3796_CR53","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.neurobiolaging.2019.05.025","volume":"81","author":"GD Manocha","year":"2019","unstructured":"Manocha GD, Floden AM, Miller NM, Smith AJ, Nagamoto-Combs K, Saito T, et al. Temporal progression of Alzheimer\u2019s disease in brains and intestines of transgenic mice. Neurobiol Aging. 2019;81:166\u201376.","journal-title":"Neurobiol Aging"},{"issue":"10","key":"3796_CR54","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1212\/WNL.0b013e3181b6bb95","volume":"73","author":"C Holmes","year":"2009","unstructured":"Holmes C, Cunningham C, Zotova E, Woolford J, Dean C, Kerr S, et al. Systemic inflammation and disease progression in Alzheimer disease. Neurology. 2009;73(10):768\u201374.","journal-title":"Neurology"},{"issue":"12","key":"3796_CR55","doi-asserted-by":"publisher","first-page":"e634","DOI":"10.1002\/ctm2.634","volume":"11","author":"JS Yu","year":"2021","unstructured":"Yu JS, Youn GS, Choi J, Kim CH, Kim BY, Yang SJ, et al. Lactobacillus lactis and Pediococcus pentosaceus-driven reprogramming of gut microbiome and metabolome ameliorates the progression of non-alcoholic fatty liver disease. Clin Transl Med. 2021;11(12):e634.","journal-title":"Clin Transl Med"},{"issue":"3","key":"3796_CR56","doi-asserted-by":"publisher","first-page":"166042","DOI":"10.1016\/j.bbadis.2020.166042","volume":"1867","author":"L Lionetto","year":"2021","unstructured":"Lionetto L, Ulivieri M, Capi M, De Bernardini D, Fazio F, Petrucca A, et al. Increased kynurenine-to-tryptophan ratio in the serum of patients infected with SARS-CoV2: an observational cohort study. Biochimica et Biophysica Acta (BBA). 2021;1867(3):166042.","journal-title":"Biochimica et Biophysica Acta (BBA)"},{"key":"3796_CR57","doi-asserted-by":"publisher","first-page":"117864691986897","DOI":"10.1177\/1178646919868978","volume":"12","author":"AA Badawy","year":"2019","unstructured":"Badawy AA, Guillemin G. The plasma [kynurenine]\/[tryptophan] ratio and indoleamine 2,3-dioxygenase: time for appraisal. Int J Tryptophan Res. 2019;12:1178646919868978.","journal-title":"Int J Tryptophan Res"},{"issue":"4","key":"3796_CR58","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/j.cell.2015.12.056","volume":"164","author":"B De Strooper","year":"2016","unstructured":"De Strooper B, Karran E. The cellular phase of Alzheimer\u2019s disease. Cell. 2016;164(4):603\u201315.","journal-title":"Cell"},{"issue":"1","key":"3796_CR59","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/s41398-019-0525-3","volume":"9","author":"J Sun","year":"2019","unstructured":"Sun J, Xu J, Ling Y, Wang F, Gong T, Yang C, et al. Fecal microbiota transplantation alleviated Alzheimer\u2019s disease-like pathogenesis in APP\/PS1 transgenic mice. Transl Psychiatry. 2019;9(1):189.","journal-title":"Transl Psychiatry"},{"issue":"2","key":"3796_CR60","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1046\/j.1471-4159.1999.0720643.x","volume":"72","author":"PS Hodgkins","year":"1999","unstructured":"Hodgkins PS, Wu HQ, Zielke HR, Schwarcz R. 2-oxoacids regulate kynurenic acid production in the rat brain: studies in vitro and in vivo. J Neurochem. 1999;72(2):643\u201351.","journal-title":"J Neurochem"},{"key":"3796_CR61","doi-asserted-by":"publisher","first-page":"110928","DOI":"10.1016\/j.mce.2020.110928","volume":"518","author":"TW Jung","year":"2020","unstructured":"Jung TW, Park J, Sun JL, Ahn SH, Abd El-Aty AM, Hacimuftuoglu A, et al. Administration of kynurenic acid reduces hyperlipidemia-induced inflammation and insulin resistance in skeletal muscle and adipocytes. Mol Cell Endocrinol. 2020;518:110928.","journal-title":"Mol Cell Endocrinol"},{"issue":"8","key":"3796_CR62","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.2174\/1381612822666151214125950","volume":"22","author":"MI Cuartero","year":"2016","unstructured":"Cuartero MI, de la Parra J, Garcia-Culebras A, Ballesteros I, Lizasoain I, Moro MA. The kynurenine pathway in the acute and chronic phases of cerebral ischemia. Curr Pharm Des. 2016;22(8):1060\u201373.","journal-title":"Curr Pharm Des"},{"key":"3796_CR63","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.3389\/fimmu.2017.01957","volume":"8","author":"E Wirthgen","year":"2017","unstructured":"Wirthgen E, Hoeflich A, Rebl A, Gunther J. Kynurenic acid: the Janus-faced role of an immunomodulatory tryptophan metabolite and its link to pathological conditions. Front Immunol. 2017;8:1957.","journal-title":"Front Immunol"},{"issue":"6","key":"3796_CR64","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1016\/j.cmet.2024.03.014","volume":"36","author":"Y Li","year":"2024","unstructured":"Li Y, Munoz-Mayorga D, Nie Y, Kang N, Tao Y, Lagerwall J, et al. Microglial lipid droplet accumulation in tauopathy brain is regulated by neuronal AMPK. Cell Metab. 2024;36(6):1351-70 e8.","journal-title":"Cell Metab"},{"key":"3796_CR65","doi-asserted-by":"publisher","first-page":"1570125","DOI":"10.3389\/fphar.2025.1570125","volume":"16","author":"WS Sarawi","year":"2025","unstructured":"Sarawi WS, Alhusaini AM, Barwaished GS, Altamimi MM, Hasan IH, Aljarboa AS, et al. Indole-3-acetic acid and chenodeoxycholic acid attenuate TLR4\/NF-kappaB signaling and endoplasmic reticulum stress in valproic acid-induced neurotoxicity. Front Pharmacol. 2025;16:1570125.","journal-title":"Front Pharmacol"},{"key":"3796_CR66","doi-asserted-by":"crossref","unstructured":"Ding Y, Yanagi K, Yang F, Callaway E, Cheng C, Hensel ME, et al. Oral supplementation of gut microbial metabolite indole-3-acetate alleviates diet-induced steatosis and inflammation in mice. Elife. 2024;12.","DOI":"10.7554\/eLife.87458.3"},{"key":"3796_CR67","doi-asserted-by":"publisher","first-page":"762580","DOI":"10.3389\/fimmu.2022.762580","volume":"13","author":"J Shen","year":"2022","unstructured":"Shen J, Yang L, You K, Chen T, Su Z, Cui Z, et al. Indole-3-acetic acid alters intestinal microbiota and alleviates ankylosing spondylitis in mice. Front Immunol. 2022;13:762580.","journal-title":"Front Immunol"},{"issue":"7","key":"3796_CR68","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1038\/nn.4030","volume":"18","author":"D Erny","year":"2015","unstructured":"Erny D, Hrabe de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015;18(7):965\u201377.","journal-title":"Nat Neurosci"},{"issue":"11","key":"3796_CR69","doi-asserted-by":"publisher","first-page":"2260","DOI":"10.1016\/j.cmet.2021.10.010","volume":"33","author":"D Erny","year":"2021","unstructured":"Erny D, Dokalis N, Mezo C, Castoldi A, Mossad O, Staszewski O, et al. Microbiota-derived acetate enables the metabolic fitness of the brain innate immune system during health and disease. Cell Metab. 2021;33(11):2260-76e7.","journal-title":"Cell Metab"},{"issue":"1","key":"3796_CR70","doi-asserted-by":"publisher","first-page":"2819","DOI":"10.1038\/s41598-022-27086-x","volume":"13","author":"ME Caetano-Silva","year":"2023","unstructured":"Caetano-Silva ME, Rund L, Hutchinson NT, Woods JA, Steelman AJ, Johnson RW. Inhibition of inflammatory microglia by dietary fiber and short-chain fatty acids. Sci Rep. 2023;13(1):2819.","journal-title":"Sci Rep"},{"issue":"4","key":"3796_CR71","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.cell.2017.07.023","volume":"170","author":"TK Ulland","year":"2017","unstructured":"Ulland TK, Song WM, Huang SC, Ulrich JD, Sergushichev A, Beatty WL, et al. TREM2 maintains microglial metabolic fitness in Alzheimer\u2019s disease. Cell. 2017;170(4):649-63 e13.","journal-title":"Cell"},{"issue":"9","key":"3796_CR72","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1016\/j.jmb.2019.03.006","volume":"431","author":"BI Aldana","year":"2019","unstructured":"Aldana BI. Microglia-specific metabolic changes in neurodegeneration. J Mol Biol. 2019;431(9):1830\u201342.","journal-title":"J Mol Biol"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-026-03796-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-026-03796-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-026-03796-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:38:10Z","timestamp":1781649490000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12974-026-03796-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":72,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3796"],"URL":"https:\/\/doi.org\/10.1186\/s12974-026-03796-1","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,24]]},"assertion":[{"value":"18 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 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 experiments were reviewed and approved by the Institutional Animal Care and Use Committee of Seoul National University (SNU IACUC; approval no. SNU-230807\u20131-2), and were conducted in accordance with institutional and national guidelines.","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":"A provisional patent application has been filed related to the content of this manuscript. The authors are listed as inventors.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"197"}}