{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T20:16:56Z","timestamp":1793132216292,"version":"4.5.0"},"reference-count":114,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Darby Rimmer MND Foundation"},{"DOI":"10.13039\/501100000833","name":"Rosetrees Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000833","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017026","name":"Spastic Paraplegia Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017026","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000406","name":"Motor Neurone Disease Association","doi-asserted-by":"publisher","award":["1122462"],"award-info":[{"award-number":["1122462"]}],"id":[{"id":"10.13039\/501100000406","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011776","name":"MND Scotland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011776","id-type":"DOI","asserted-by":"publisher"}]},{"name":"South London and Maudsley NHS Foundation Trust, MRC","award":["MR\/Z505705\/1"],"award-info":[{"award-number":["MR\/Z505705\/1"]}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UK Dementia Research Institute through UK DRI Ltd."},{"DOI":"10.13039\/100013869","name":"Dementia Consortium","doi-asserted-by":"publisher","award":["1819242"],"award-info":[{"award-number":["1819242"]}],"id":[{"id":"10.13039\/100013869","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MRC","award":["MR\/Z505705\/1"],"award-info":[{"award-number":["MR\/Z505705\/1"]}]},{"name":"Darby Rimmer MND Foundation, LifeArc","award":["RE23378"],"award-info":[{"award-number":["RE23378"]}]},{"name":"NIHR Maudsley Biomedical Research Centre, ALS Association Milton Safenowitz Research Fellowship","award":["RE19765"],"award-info":[{"award-number":["RE19765"]}]},{"DOI":"10.13039\/501100000406","name":"Motor Neurone Disease Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000406","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000406","name":"MND Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000406","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute for Health and Care Research (NIHR) as a Pre-Doctoral Research Fellow","award":["303476"],"award-info":[{"award-number":["303476"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gut microbiome disturbances have been proposed as contributors to amyotrophic lateral sclerosis (ALS), a multisystem neurodegenerative disorder characterised by motor neuron loss, extra-motor symptoms, and rapid progression. Mechanistic links between dysbiosis, epithelial and blood\u2013brain barrier dysfunction, metabolic imbalance, and immune activation have been suggested, but causality remains unresolved. We conducted a systematic review to evaluate the evidence supporting microbiome involvement in ALS pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched PubMed, Medline, Embase, Scopus, Semantic Scholar, and Google Scholar (Nov 23, 2025) for human and ALS-relevant animal studies assessing bacterial microbiota, gut or blood\u2013brain barrier integrity, microbial metabolites, or immune pathways. No language or date restrictions were applied. Studies were screened according to predefined criteria, and quality was assessed using QUADAS-2. Owing to the heterogeneity of study designs and sequencing approaches, findings were synthesised narratively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>61 of 2,397 studies met inclusion criteria. Across human cohorts, ALS was consistently associated with reduced microbial diversity, shifts in key taxa, and disruption of microbial pathways regulating short-chain fatty acids, nicotinamide metabolism, and inflammatory signalling. Several mechanistic animal studies demonstrated that microbiota manipulation, through antibiotics, faecal microbiota transfer, or supplementation with protective taxa, modulated motor function, microglial activation, gut permeability, and survival, indicating that dysbiosis can influence disease trajectories. Conversely, longitudinal human data showed that dysbiosis often emerged alongside worsening physical function, gastrointestinal dysmotility, weight loss, and changes in dietary intake, suggesting secondary effects of disease progression. Integrative multi-omics studies linked microbial alterations with systemic cytokine profiles, metabolic stress pathways, and CNS immune phenotypes, reinforcing a bidirectional gut\u2013brain axis. However, the predominance of cross-sectional designs and small sample sizes substantially limits causal inference.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Current evidence supports a model in which gut dysbiosis interacts with ALS via barrier failure, metabolic disruption, and immune dysregulation, but does not establish dysbiosis as a primary cause of disease. Preclinical findings highlight microbiome-derived mechanisms with disease-modifying potential, yet human data largely indicate association rather than initiation. Clarifying temporal relationships will require longitudinal, multi-modal studies, integration with pre-symptomatic cohorts, and controlled interventional trials. Microbiome-targeted therapies remain a promising but unproven avenue for ALS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1774417","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:43:14Z","timestamp":1776058994000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Gut microbiota and ALS: cause, consequence or correlation? - a systematic review"],"prefix":"10.3389","volume":"20","author":[{"given":"Debarghya Kumar","family":"Chakraborty","sequence":"first","affiliation":[{"name":"King\u2019s College Hospital, NHS Foundation Trust","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Triparna","family":"Roy","sequence":"additional","affiliation":[{"name":"King\u2019s College London, Institute of Psychiatry, Psychology & Neuroscience","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyuan Thieu","family":"Ngo","sequence":"additional","affiliation":[{"name":"Australian Institute of Bioengineering and Nanotechnology, The University of Queensland","place":["St Lucia, QLD, Australia"]},{"name":"Department NA Murdoch University","place":["Perth, WA, Australia"]},{"name":"The University of Queensland Centre for Motor Neuron Disease Research, The University of Queensland","place":["St Lucia, QLD, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammar","family":"Al-Chalabi","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospital, NHS Foundation Trust","place":["London, United Kingdom"]},{"name":"King\u2019s College London, Institute of Psychiatry, Psychology & Neuroscience","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Al Khleifat","sequence":"additional","affiliation":[{"name":"King\u2019s College London, Institute of Psychiatry, Psychology & Neuroscience","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.ibneur.2025.05.014","article-title":"The microbial guardians: unveiling the role of gut microbiota in shaping neurodegenerative disease","volume":"19","author":"Abou Izzeddine","year":"2025","journal-title":"IBRO Neurosci. 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