{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T01:51:23Z","timestamp":1780969883232,"version":"3.54.1"},"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Race Against Dementia, UK","award":["Charity Number: 1165559"],"award-info":[{"award-number":["Charity Number: 1165559"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Idiopathic normal pressure hydrocephalus (iNPH), a leading cause of reversible dementia in older adults, is marked by ventriculomegaly, gait disturbances, cognitive decline, and urinary incontinence. Emerging evidence suggests that gut dysbiosis (microbial imbalance) may influence neuroinflammation and cerebrospinal fluid dynamics, potentially contributing to glymphatic system dysfunction and ventricular enlargement. This study used shotgun metagenomics to analyze the gut microbiome in iNPH patients (n\u2009=\u200918) compared to healthy controls (n\u2009=\u200950), individuals with ventriculomegaly but no iNPH symptoms (n\u2009=\u200950), and Alzheimer\u2019s disease patients (n\u2009=\u200950). Microbiome analysis showed an enrichment of species previously linked to various disease states, such as <jats:italic><jats:italic>Enterocloster bolteae<\/jats:italic><\/jats:italic> and <jats:italic><jats:italic>Ruminococcus gnavus<\/jats:italic><\/jats:italic>, indicating general dysbiosis. In contrast, enrichment of specific taxa, including <jats:italic><jats:italic>Evtepia gabavorous<\/jats:italic><\/jats:italic> and <jats:italic><jats:italic>Cuneatibacter sp.<\/jats:italic><\/jats:italic>, were specifically associated with iNPH clinical traits, pointing to possible disease-specific microbial markers. Functional analysis showed enrichment of pathways related to carbohydrate and amino acid metabolism, including the S-adenosyl-L-methionine superpathway, implicating inflammatory and immune processes. These findings suggest distinct gut microbiome signatures in iNPH, offering insights into potential gut-brain interactions that may contribute to the disorder\u2019s pathophysiology and highlighting possible targets for future therapeutic strategies.<\/jats:p>","DOI":"10.1371\/journal.pone.0330251","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T17:23:13Z","timestamp":1757956993000},"page":"e0330251","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Gut microbiome signatures in iNPH: Insights from a shotgun metagenomics study"],"prefix":"10.1371","volume":"20","author":[{"given":"Rahel","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Chevalier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silas","family":"Kieser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3749-2988","authenticated-orcid":true,"given":"Moira","family":"Marizzoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Paquis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Armand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2274-5129","authenticated-orcid":true,"given":"Max","family":"Scheffler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Allali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Assal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahan","family":"Momjian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7075-7082","authenticated-orcid":true,"given":"Giovanni B.","family":"Frisoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"issue":"4","key":"pone.0330251.ref001","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0022-510X(65)90016-X","article-title":"The special clinical problem of symptomatic hydrocephalus with normal cerebrospinal fluid pressure. Observations on cerebrospinal fluid hydrodynamics","volume":"2","author":"S Hakim","year":"1965","journal-title":"J Neurol Sci"},{"issue":"5","key":"pone.0330251.ref002","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0217705","article-title":"Prevalence of idiopathic normal pressure hydrocephalus: A prospective, population-based study","volume":"14","author":"J Andersson","year":"2019","journal-title":"PLoS One"},{"issue":"6","key":"pone.0330251.ref003","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1016\/j.wneu.2015.07.005","article-title":"Epidemiology of Idiopathic Normal Pressure Hydrocephalus: A Systematic Review of the Literature","volume":"84","author":"R Mart\u00edn-L\u00e1ez","year":"2015","journal-title":"World Neurosurg"},{"issue":"5","key":"pone.0330251.ref004","doi-asserted-by":"crossref","first-page":"197","DOI":"10.2176\/nmc.48.197","article-title":"Prevalence of idiopathic normal-pressure hydrocephalus in the elderly population of a Japanese rural community","volume":"48","author":"K Hiraoka","year":"2008","journal-title":"Neurol Med Chir (Tokyo)"},{"issue":"1","key":"pone.0330251.ref005","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12987-018-0090-9","article-title":"Paradigm-shift: radiological changes in the asymptomatic iNPH-patient to be: an observational study","volume":"15","author":"DC Engel","year":"2018","journal-title":"Fluids Barriers CNS"},{"key":"pone.0330251.ref006","doi-asserted-by":"crossref","first-page":"117166","DOI":"10.1016\/j.jns.2020.117166","article-title":"A multi-center, prospective study on the progression rate of asymptomatic ventriculomegaly with features of idiopathic normal pressure hydrocephalus on magnetic resonance imaging to idiopathic normal pressure hydrocephalus","volume":"419","author":"L Kimihira","year":"2020","journal-title":"J Neurol Sci"},{"issue":"5","key":"pone.0330251.ref007","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1111\/ane.13710","article-title":"Prevalence and development of idiopathic normal pressure hydrocephalus: A 16-year longitudinal study in Japan","volume":"146","author":"C Iseki","year":"2022","journal-title":"Acta Neurol Scand"},{"issue":"11","key":"pone.0330251.ref008","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1002\/mds.28251","article-title":"Gaps, Controversies, and Proposed Roadmap for Research in Normal Pressure Hydrocephalus","volume":"35","author":"A Fasano","year":"2020","journal-title":"Mov Disord"},{"issue":"3","key":"pone.0330251.ref009","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1111\/ene.13543","article-title":"Brain comorbidities in normal pressure hydrocephalus","volume":"25","author":"G Allali","year":"2018","journal-title":"Eur J Neurol"},{"issue":"4","key":"pone.0330251.ref010","doi-asserted-by":"crossref","DOI":"10.3171\/2020.7.FOCUS20466","article-title":"Risk factors, comorbidities, quality of life, and complications after surgery in idiopathic normal pressure hydrocephalus: review of the INPH-CRasH study","volume":"49","author":"H Israelsson","year":"2020","journal-title":"Neurosurg Focus"},{"issue":"3","key":"pone.0330251.ref011","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.molmed.2019.11.008","article-title":"Glymphatic System Impairment in Alzheimer\u2019s Disease and Idiopathic Normal Pressure Hydrocephalus","volume":"26","author":"BC Reeves","year":"2020","journal-title":"Trends Mol Med"},{"issue":"21","key":"pone.0330251.ref012","doi-asserted-by":"crossref","first-page":"4631","DOI":"10.3390\/nu15214631","article-title":"Understanding the Gut-Brain Axis and Its Therapeutic Implications for Neurodegenerative Disorders","volume":"15","author":"Y Zheng","year":"2023","journal-title":"Nutrients"},{"issue":"11","key":"pone.0330251.ref013","doi-asserted-by":"crossref","first-page":"9577","DOI":"10.3390\/ijms24119577","article-title":"Neurodegenerative and neurodevelopmental diseases and the gut-brain axis: the potential of therapeutic targeting of the microbiome","volume":"24","author":"B Bicknell","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0330251.ref014","doi-asserted-by":"crossref","first-page":"6958","DOI":"10.1038\/s41467-022-34667-x","article-title":"Metagenomics of Parkinson\u2019s disease implicates the gut microbiome in multiple disease mechanisms","volume":"13","author":"ZD Wallen","year":"2022","journal-title":"Nat Commun"},{"issue":"1","key":"pone.0330251.ref015","first-page":"1","article-title":"Meta-analysis of the Parkinson\u2019s disease gut microbiome suggests alterations linked to intestinal inflammation","volume":"7","author":"S Romano","year":"2021","journal-title":"NPJ Parkinson\u2019s Disease"},{"issue":"9","key":"pone.0330251.ref016","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1093\/brain\/awab156","article-title":"The role of gut dysbiosis in Parkinson\u2019s disease: mechanistic insights and therapeutic options","volume":"144","author":"Q Wang","year":"2021","journal-title":"Brain J Neurol"},{"issue":"3","key":"pone.0330251.ref017","doi-asserted-by":"crossref","first-page":"412","DOI":"10.3390\/nu16030412","article-title":"The Role of Diet and Gut Microbiota in Alzheimer\u2019s Disease","volume":"16","author":"DMS Dissanayaka","year":"2024","journal-title":"Nutrients"},{"issue":"1","key":"pone.0330251.ref018","doi-asserted-by":"crossref","first-page":"13537","DOI":"10.1038\/s41598-017-13601-y","article-title":"Gut microbiome alterations in Alzheimer\u2019s disease","volume":"7","author":"NM Vogt","year":"2017","journal-title":"Scientific Reports"},{"issue":"1","key":"pone.0330251.ref019","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s13195-023-01218-5","article-title":"A peripheral signature of Alzheimer\u2019s disease featuring microbiota-gut-brain axis markers","volume":"15","author":"M Marizzoni","year":"2023","journal-title":"Alzheimers Res Ther"},{"issue":"2","key":"pone.0330251.ref020","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1097\/WAD.0000000000000613","article-title":"Gut Microbiome Changes in Patients With Idiopathic Normal Pressure Hydrocephalus","volume":"38","author":"E Brandt","year":"2024","journal-title":"Alzheimer Dis Assoc Disord"},{"issue":"1","key":"pone.0330251.ref021","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1038\/s41598-021-82726-y","article-title":"Comparison between 16S rRNA and shotgun sequencing data for the taxonomic characterization of the gut microbiota","volume":"11","author":"F Durazzi","year":"2021","journal-title":"Sci Rep"},{"key":"pone.0330251.ref022","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.clineuro.2017.06.001","article-title":"A combined cognitive and gait quantification to identify normal pressure hydrocephalus from its mimics: The Geneva\u2019s protocol","volume":"160","author":"G Allali","year":"2017","journal-title":"Clin Neurol Neurosurg"},{"key":"pone.0330251.ref023","doi-asserted-by":"crossref","DOI":"10.1227\/01.NEU.0000168185.29659.C5","article-title":"Diagnosing idiopathic normal-pressure hydrocephalus","volume":"57","author":"N Relkin","year":"2005","journal-title":"Neurosurgery"},{"issue":"2","key":"pone.0330251.ref024","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s00259-019-04536-9","article-title":"The A\/T\/N model applied through imaging biomarkers in a memory clinic","volume":"47","author":"A Dodich","year":"2020","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"6","key":"pone.0330251.ref025","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1136\/jnnp-2022-330619","article-title":"Plasma biomarkers for Alzheimer\u2019s disease: a field-test in a memory clinic","volume":"94","author":"D Altomare","year":"2023","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"pone.0330251.ref026","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.neuroimage.2013.05.007","article-title":"Brain morphometry reproducibility in multi-center 3 T MRI studies: a comparison of cross-sectional and longitudinal segmentations","volume":"83","author":"J Jovicich","year":"2013","journal-title":"NeuroImage"},{"issue":"4","key":"pone.0330251.ref027","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.neuroimage.2011.06.080","article-title":"A comprehensive testing protocol for MRI neuroanatomical segmentation techniques: Evaluation of a novel lateral ventricle segmentation method","volume":"58","author":"MJ Kempton","year":"2011","journal-title":"NeuroImage"},{"issue":"2","key":"pone.0330251.ref028","doi-asserted-by":"crossref","DOI":"10.1002\/imt2.107","article-title":"Ultrafast one-pass FASTQ data preprocessing, quality control, and deduplication using fastp","volume":"2","author":"S Chen","year":"2023","journal-title":"Imeta"},{"issue":"1","key":"pone.0330251.ref029","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1186\/s13059-019-1891-0","article-title":"Improved metagenomic analysis with Kraken 2","volume":"20","author":"DE Wood","year":"2019","journal-title":"Genome Biol"},{"key":"pone.0330251.ref030","article-title":"Pangenome databases improve host removal and mycobacteria classification from clinical metagenomic data","volume":"13","author":"MB Hall","year":"2024","journal-title":"GigaScience"},{"issue":"11","key":"pone.0330251.ref031","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1038\/s41587-023-01688-w","article-title":"Extending and improving metagenomic taxonomic profiling with uncharacterized species using MetaPhlAn 4","volume":"41","author":"A Blanco-M\u00edguez","year":"2023","journal-title":"Nat Biotechnol"},{"key":"pone.0330251.ref032","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.65088","article-title":"Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3","volume":"10","author":"F Beghini","year":"2021","journal-title":"eLife"},{"key":"pone.0330251.ref033","doi-asserted-by":"crossref","first-page":"33","DOI":"10.12688\/f1000research.29032.2","article-title":"Sustainable data analysis with Snakemake","volume":"10","author":"F M\u00f6lder","year":"2021","journal-title":"F1000Res"},{"issue":"63","key":"pone.0330251.ref034","doi-asserted-by":"crossref","first-page":"3201","DOI":"10.21105\/joss.03201","article-title":"microViz: an R package for microbiome data visualization and statistics","volume":"6","author":"D Barnett","year":"2021","journal-title":"JOSS"},{"issue":"11","key":"pone.0330251.ref035","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1009442","article-title":"Multivariable association discovery in population-scale meta-omics studies","volume":"17","author":"H Mallick","year":"2021","journal-title":"PLoS Comput Biol"},{"issue":"1","key":"pone.0330251.ref036","doi-asserted-by":"crossref","first-page":"3514","DOI":"10.1038\/s41467-020-17041-7","article-title":"Analysis of compositions of microbiomes with bias correction","volume":"11","author":"H Lin","year":"2020","journal-title":"Nat Commun"},{"issue":"8","key":"pone.0330251.ref037","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"E Bolyen","year":"2019","journal-title":"Nat Biotechnol"},{"issue":"1","key":"pone.0330251.ref038","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/s41467-022-28034-z","article-title":"Microbiome differential abundance methods produce different results across 38 datasets","volume":"13","author":"JT Nearing","year":"2022","journal-title":"Nat Commun"},{"issue":"9","key":"pone.0330251.ref039","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s12264-022-00873-2","article-title":"Cognitive impairment in idiopathic normal pressure hydrocephalus","volume":"38","author":"H Xiao","year":"2022","journal-title":"Neurosci Bull"},{"key":"pone.0330251.ref040","doi-asserted-by":"crossref","first-page":"6445","DOI":"10.1212\/WNL.0000000000206469","article-title":"Patient-reported symptoms in idiopathic normal pressure hydrocephalus (P2-3.008)","volume":"102","author":"Q Hu","year":"2024","journal-title":"Neurology"},{"issue":"1","key":"pone.0330251.ref041","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41522-024-00567-9","article-title":"A population-scale analysis of 36 gut microbiome studies reveals universal species signatures for common diseases","volume":"10","author":"W Sun","year":"2024","journal-title":"NPJ Biofilms Microbiomes"},{"issue":"7907","key":"pone.0330251.ref042","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/s41586-022-04567-7","article-title":"Environmental factors shaping the gut microbiome in a Dutch population","volume":"604","author":"R Gacesa","year":"2022","journal-title":"Nature"},{"issue":"1","key":"pone.0330251.ref043","doi-asserted-by":"crossref","first-page":"6818","DOI":"10.1038\/s41467-022-34405-3","article-title":"Faecal microbiome-based machine learning for multi-class disease diagnosis","volume":"13","author":"Q Su","year":"2022","journal-title":"Nat Commun"},{"issue":"1","key":"pone.0330251.ref044","doi-asserted-by":"crossref","first-page":"4635","DOI":"10.1038\/s41467-020-18476-8","article-title":"A predictive index for health status using species-level gut microbiome profiling","volume":"11","author":"VK Gupta","year":"2020","journal-title":"Nat Commun"},{"issue":"6","key":"pone.0330251.ref045","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1101\/gr.278637.123","article-title":"Global compositional and functional states of the human gut microbiome in health and disease","volume":"34","author":"S Lee","year":"2024","journal-title":"Genome Res"},{"issue":"2","key":"pone.0330251.ref046","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41591-020-01183-8","article-title":"Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals","volume":"27","author":"F Asnicar","year":"2021","journal-title":"Nat Med"},{"issue":"12","key":"pone.0330251.ref047","doi-asserted-by":"crossref","first-page":"2802","DOI":"10.1097\/MIB.0000000000000972","article-title":"A single species of Clostridium subcluster XIVa decreased in ulcerative colitis patients","volume":"22","author":"K Takeshita","year":"2016","journal-title":"Inflamm Bowel Dis"},{"issue":"8","key":"pone.0330251.ref048","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1016\/j.cell.2024.03.014","article-title":"Gut microbiome and metabolome profiling in Framingham heart study reveals cholesterol-metabolizing bacteria","volume":"187","author":"C Li","year":"2024","journal-title":"Cell"},{"issue":"6","key":"pone.0330251.ref049","article-title":"A multi-omics analysis for the prediction of neurocognitive disorders risk among the elderly in Macao","volume":"12","author":"Y Han","year":"2022","journal-title":"Clin Transl Med"},{"issue":"2","key":"pone.0330251.ref050","doi-asserted-by":"crossref","DOI":"10.1093\/femsre\/fuad014","article-title":"Ruminococcus gnavus: friend or foe for human health","volume":"47","author":"EH Crost","year":"2023","journal-title":"FEMS Microbiol Rev"},{"issue":"7","key":"pone.0330251.ref051","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1128\/JCM.00128-12","article-title":"High mortality associated with Catabacter hongkongensis bacteremia","volume":"50","author":"SKP Lau","year":"2012","journal-title":"J Clin Microbiol"},{"issue":"5","key":"pone.0330251.ref052","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s10096-005-1334-6","article-title":"Clostridium clostridioforme: a mixture of three clinically important species","volume":"24","author":"SM Finegold","year":"2005","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"pone.0330251.ref053","doi-asserted-by":"crossref","first-page":"102838","DOI":"10.1016\/j.anaerobe.2024.102838","article-title":"Hungatella hathewayi bacteremia due to acute appendicitis: A case report and a narrative review","volume":"86","author":"E Bou Sanayeh","year":"2024","journal-title":"Anaerobe"},{"issue":"3","key":"pone.0330251.ref054","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/s41564-018-0307-3","article-title":"GABA-modulating bacteria of the human gut microbiota","volume":"4","author":"P Strandwitz","year":"2019","journal-title":"Nat Microbiol"},{"issue":"7","key":"pone.0330251.ref055","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1136\/gutjnl-2020-322670","article-title":"Long-term dietary patterns are associated with pro-inflammatory and anti-inflammatory features of the gut microbiome","volume":"70","author":"LA Bolte","year":"2021","journal-title":"Gut"},{"issue":"1","key":"pone.0330251.ref056","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1038\/s41467-017-02109-8","article-title":"Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus","volume":"8","author":"CD Owen","year":"2017","journal-title":"Nat Commun"},{"issue":"4","key":"pone.0330251.ref057","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1152\/physrev.00018.2018","article-title":"The Microbiota-Gut-Brain Axis","volume":"99","author":"JF Cryan","year":"2019","journal-title":"Physiol Rev"},{"issue":"263","key":"pone.0330251.ref058","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3009759","article-title":"The gut microbiota influences blood-brain barrier permeability in mice","volume":"6","author":"V Braniste","year":"2014","journal-title":"Sci Transl Med"},{"issue":"17","key":"pone.0330251.ref059","article-title":"Gut microbiota regulates blood-cerebrospinal fluid barrier function and A\u03b2 pathology","volume":"42","author":"J Xie","year":"2023","journal-title":"EMBO J"},{"issue":"1","key":"pone.0330251.ref060","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s12987-023-00472-x","article-title":"Levels of inflammatory cytokines MCP-1, CCL4, and PD-L1 in CSF differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases","volume":"20","author":"M Braun","year":"2023","journal-title":"Fluids Barriers CNS"},{"key":"pone.0330251.ref061","article-title":"Mechanistic insights into gut microbiome dysbiosis-mediated neuroimmune dysregulation and protein misfolding and clearance in the pathogenesis of chronic neurodegenerative disorders","author":"P Padhi","year":"2022","journal-title":"Frontiers in Neuroscience"},{"issue":"11","key":"pone.0330251.ref062","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1517\/17425255.2010.522177","article-title":"The biochemical and toxicological significance of hypermethionemia: new insights and clinical relevance","volume":"6","author":"JT Dever","year":"2010","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"pone.0330251.ref063","doi-asserted-by":"crossref","first-page":"577843","DOI":"10.1016\/j.jneuroim.2022.577843","article-title":"L-methionine enhances neuroinflammation and impairs neurogenesis: implication for Alzheimer\u2019s disease","volume":"366","author":"A Alachkar","year":"2022","journal-title":"J Neuroimmunol"},{"issue":"4","key":"pone.0330251.ref064","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1172\/JCI118862","article-title":"Demyelination of the brain is associated with methionine adenosyltransferase I\/III deficiency","volume":"98","author":"ME Chamberlin","year":"1996","journal-title":"J Clin Invest"},{"key":"pone.0330251.ref065","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuint.2017.10.011","article-title":"Dysregulation of methionine metabolism in multiple sclerosis","volume":"112","author":"NK Singhal","year":"2018","journal-title":"Neurochem Int"},{"issue":"3","key":"pone.0330251.ref066","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.ymgme.2012.08.002","article-title":"Methionine adenosyltransferase I\/III deficiency: neurological manifestations and relevance of S-adenosylmethionine","volume":"107","author":"M Furujo","year":"2012","journal-title":"Mol Genet Metab"},{"issue":"2","key":"pone.0330251.ref067","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.molcel.2020.03.004","article-title":"Methyl-metabolite depletion elicits adaptive responses to support heterochromatin stability and epigenetic persistence","volume":"78","author":"SA Haws","year":"2020","journal-title":"Molecular Cell"},{"issue":"5","key":"pone.0330251.ref068","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1021\/acs.estlett.9b00142","article-title":"Allantoin as a marker of oxidative stress: inter- and intraindividual variability in urinary concentrations in healthy individuals","volume":"6","author":"MP Martinez-Moral","year":"2019","journal-title":"Environ Sci Technol Lett"},{"issue":"8","key":"pone.0330251.ref069","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1089\/ars.2008.2364","article-title":"Allantoin in human plasma, serum, and nasal-lining fluids as a biomarker of oxidative stress: avoiding artifacts and establishing real in vivo concentrations","volume":"11","author":"J Gruber","year":"2009","journal-title":"Antioxid Redox Signal"},{"issue":"4","key":"pone.0330251.ref070","doi-asserted-by":"crossref","first-page":"325","DOI":"10.5607\/en.2015.24.4.325","article-title":"The Role of Oxidative Stress in Neurodegenerative Diseases","volume":"24","author":"GH Kim","year":"2015","journal-title":"Exp Neurobiol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0330251","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T17:23:23Z","timestamp":1757957003000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0330251"}},"subtitle":[],"editor":[{"given":"Jing A.","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,15]]},"references-count":70,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0330251","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,15]]}}}