{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:02:12Z","timestamp":1790182932577,"version":"4.1.0"},"reference-count":39,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"unspecified","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,9,10]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Traumatic brain injury (TBI) is a major cause of long-term disability worldwide, but the pathophysiological mechanisms underlying its chronic sequelae remain incompletely understood. In addition to persistent neuroinflammation, evidence suggests that dysregulation of the gut microbiota influences brain recovery. The OVERCOME-TBI study investigates the long-term functional, cognitive, imaging, biochemical and gastrointestinal outcomes after TBI of all severities, with the aim of identifying biomarkers and microbiome signatures associated with progressive neurodegeneration and poor recovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      This is a prospective, observational study with long-term follow-up of two previously established TBI cohorts\u2014the Evidence-based Diagnostic and Treatment Planning Solution for Traumatic Brain Injuries (TBIcare; recruited 2011\u20132013)\u2009and the Pathophysiological Characterisation of Severe TBI (PACoS-TBI; recruited 2020\u20132023). The design combines prospectively collected acute and subacute data from the original cohorts with new cross-sectional assessments performed at chronic time points (2\u20135\u2009and 12\u201315 years post-injury). Participants are re-contacted and re-consented for these chronic-phase assessments. Up to 160 patients with TBI and 30 orthopaedic injury controls will undergo multimodal examinations: neurological and neuropsychological testing, advanced MRI including multishell diffusion and resting-state functional MRI, positron emission tomography (PET) with the radioligand [\n                      <jats:sup>11<\/jats:sup>\n                      C]PK11195, blood-based proteomics, lipidomics, metabolomics, faecal and intestinal microbiome profiling and colonoscopy biopsies. Moreover, 10 patients with multiple sclerosis (as a positive control group) will undergo PET imaging and sampling for blood biomarkers. Primary outcomes include neuroinflammatory burden (biochemical and PET), longitudinal functional outcomes (Glasgow Outcome Scale Extended) and gut microbiota composition. Statistical modelling, including regression models and machine learning, will be applied to identify predictors of outcome and disease progression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval has been obtained from the Ethical Committee of the Wellbeing Services County of Southwest Finland. Written informed consent will be obtained from all participants. The results will be disseminated through peer-reviewed publications, conference presentations and stakeholder engagement, with the aim of developing personalised diagnostics and novel therapeutic targets to alleviate the chronic consequences of TBI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06927063\">NCT06927063<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-120552","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:10:59Z","timestamp":1790179859000},"page":"e120552","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Long-term recovery and microbiota\u2013gut\u2013brain axis disruption after traumatic brain injury (OVERCOME-TBI): protocol for a prospective, observational clinical study"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct06927063","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06927063","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06927063","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Matti","family":"Artosalo","sequence":"first","affiliation":[{"name":"Abdominal Centre \u2013 Gastroenterology, University of Turku and Turku University Hospital, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"\u00d6stberg","sequence":"additional","affiliation":[{"name":"Neurocenter, Department of Neurosurgery and Turku Brain Injury Center, Turku University Hospital, Turku, Finland"},{"name":"Clinical Neurosciences, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli","family":"Tenovuo","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Roine","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrbod","family":"Mohammadian","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences, University of Turku, Turku, Finland"},{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teemu","family":"Kallonen","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Turku Clinical Microbiome Bank, Turku University Hospital, Turku, Finland"},{"name":"Institute of Biomedicine, University of Turku, Turku, Finland"},{"name":"Microbe Centre, University of Turku and Wellbeing Services County of Southwest Finland, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimmo","family":"Salminen","sequence":"additional","affiliation":[{"name":"Abdominal Centre \u2013 Gastroenterology, University of Turku and Turku University Hospital, Turku, Finland"},{"name":"Microbe Centre, University of Turku and Wellbeing Services County of Southwest Finland, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teppo","family":"Stenholm","sequence":"additional","affiliation":[{"name":"Abdominal Centre \u2013 Gastroenterology, University of Turku and Turku University Hospital, Turku, Finland"},{"name":"Microbe Centre, University of Turku and Wellbeing Services County of Southwest Finland, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Hakanen","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Turku Clinical Microbiome Bank, Turku University Hospital, Turku, Finland"},{"name":"Institute of Biomedicine, University of Turku, Turku, Finland"},{"name":"Microbe Centre, University of Turku and Wellbeing Services County of Southwest Finland, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teija","family":"Sainio","sequence":"additional","affiliation":[{"name":"Department of Medical Physics, University of Turku and Turku University Hospital, Turku, Finland"},{"name":"Department of Radiology, Turku University and Turku University Hospital, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussi","family":"Hirvonen","sequence":"additional","affiliation":[{"name":"Department of Radiology, Turku University and Turku University Hospital, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex M","family":"Dickens","sequence":"additional","affiliation":[{"name":"Turku Bioscience Centre, University of Turku and \u00c5bo Akademi University, Turku, Finland"},{"name":"Department of Chemistry, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matej","family":"Ore\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Turku Bioscience Centre, University of Turku and \u00c5bo Akademi University, Turku, Finland"},{"name":"School of Medical Sciences, Faculty of Medicine and Health, \u00d6rebro University, \u00d6rebro, Sweden"},{"name":"Department of Life Technologies, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2190-9278","authenticated-orcid":false,"given":"Andr\u00e1s","family":"B\u00fcki","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, Faculty of Medicine and Health, \u00d6rebro University, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuulia","family":"Hy\u00f6tyl\u00e4inen","sequence":"additional","affiliation":[{"name":"School of Science and Technology, \u00d6rebro University, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3228-9692","authenticated-orcid":false,"given":"David","family":"Menon","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6044-9035","authenticated-orcid":false,"given":"Virginia","family":"Newcombe","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-C\u00e9cile","family":"Chiollaz","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Charles","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8587-3614","authenticated-orcid":false,"given":"Stefania","family":"Mondello","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Airas","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences, University of Turku, Turku, Finland"},{"name":"Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5925-5193","authenticated-orcid":false,"given":"Jussi P","family":"Posti","sequence":"additional","affiliation":[{"name":"Neurocenter, Department of Neurosurgery and Turku Brain Injury Center, Turku University Hospital, Turku, Finland"},{"name":"Clinical Neurosciences, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"2026092309101969000_16.9.e120552.1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30371-X"},{"key":"2026092309101969000_16.9.e120552.2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30279-X"},{"key":"2026092309101969000_16.9.e120552.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.10.019"},{"key":"2026092309101969000_16.9.e120552.4","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2014.3715"},{"key":"2026092309101969000_16.9.e120552.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.07.010"},{"key":"2026092309101969000_16.9.e120552.6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI76304"},{"key":"2026092309101969000_16.9.e120552.7","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3346"},{"key":"2026092309101969000_16.9.e120552.8","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.10.066"},{"key":"2026092309101969000_16.9.e120552.9","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1097\/SHK.0000000000001278","article-title":"Complex Feed-Forward and Feedback Mechanisms Underlie the Relationship Between Traumatic Brain Injury and the Gut-Microbiota-Brain Axis","volume":"52","author":"Patterson","year":"2019","journal-title":"Shock"},{"key":"2026092309101969000_16.9.e120552.10","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.bbi.2017.05.009","article-title":"The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease","volume":"66","author":"Sundman","year":"2017","journal-title":"Brain Behav Immun"},{"key":"2026092309101969000_16.9.e120552.11","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003912"},{"key":"2026092309101969000_16.9.e120552.12","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009985"},{"key":"2026092309101969000_16.9.e120552.13","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac126"},{"key":"2026092309101969000_16.9.e120552.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.09.018"},{"key":"2026092309101969000_16.9.e120552.15","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2015.53"},{"key":"2026092309101969000_16.9.e120552.16","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuroimage.2008.04.035","article-title":"Reference tissue kinetics extraction from [11C]-(R)-PK11195 scans on the high resolution research tomograph (HRRT)","volume":"41","author":"Hinz","year":"2008","journal-title":"Neuroimage"},{"key":"2026092309101969000_16.9.e120552.17","first-page":"158","article-title":"Reference and target region modeling of [11C]-(R)-PK11195 brain studies","volume":"48","author":"Turkheimer","year":"2007","journal-title":"J Nucl Med"},{"key":"2026092309101969000_16.9.e120552.18","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.59"},{"key":"2026092309101969000_16.9.e120552.19","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.113.131698"},{"key":"2026092309101969000_16.9.e120552.20","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199609000-00008"},{"key":"2026092309101969000_16.9.e120552.21","doi-asserted-by":"crossref","first-page":"26175","DOI":"10.1021\/acs.analchem.5c05322","article-title":"The SIMPLIFY Protocol: A Monophasic Extraction System Suitable for Exposomics, Metabolomics, Lipidomics, and Proteomics Research","volume":"97","author":"Nguyen","year":"2025","journal-title":"Anal Chem"},{"key":"2026092309101969000_16.9.e120552.22","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-021-23953-9","article-title":"Ion identity molecular networking for mass spectrometry-based metabolomics in the GNPS environment","volume":"12","author":"Schmid","year":"2021","journal-title":"Nat Commun"},{"key":"2026092309101969000_16.9.e120552.23","doi-asserted-by":"crossref","DOI":"10.1186\/s13321-016-0115-9","article-title":"MetFrag relaunched: incorporating strategies beyond in silico fragmentation","volume":"8","author":"Ruttkies","year":"2016","journal-title":"J Cheminform"},{"key":"2026092309101969000_16.9.e120552.24","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac313"},{"key":"2026092309101969000_16.9.e120552.25","doi-asserted-by":"crossref","DOI":"10.1186\/s12859-025-06194-1","article-title":"An evaluation methodology for machine learning-based tandem mass spectra similarity prediction","volume":"26","author":"Strobel","year":"2025","journal-title":"BMC Bioinformatics"},{"key":"2026092309101969000_16.9.e120552.26","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/s41564-023-01575-9","article-title":"microbeMASST: a taxonomically informed mass spectrometry search tool for microbial metabolomics data","volume":"9","author":"Zuffa","year":"2024","journal-title":"Nat Microbiol"},{"key":"2026092309101969000_16.9.e120552.27","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01690-2"},{"key":"2026092309101969000_16.9.e120552.28","doi-asserted-by":"crossref","DOI":"10.1128\/spectrum.02932-23","article-title":"High-throughput DNA extraction strategy for fecal microbiome studies","volume":"12","author":"Isok\u00e4\u00e4nt\u00e4","year":"2024","journal-title":"Microbiol Spectr"},{"key":"2026092309101969000_16.9.e120552.29","doi-asserted-by":"publisher","DOI":"10.1080\/00365521.2018.1444788."},{"key":"2026092309101969000_16.9.e120552.30","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.3c04436"},{"key":"2026092309101969000_16.9.e120552.31","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0029-9"},{"key":"2026092309101969000_16.9.e120552.32","doi-asserted-by":"publisher","DOI":"10.1136\/gut.40.6.782"},{"key":"2026092309101969000_16.9.e120552.33","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.953196","article-title":"Diet, microbiota, and the mucus layer: The guardians of our health","volume":"13","author":"Suriano","year":"2022","journal-title":"Front Immunol"},{"key":"2026092309101969000_16.9.e120552.34","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-303207"},{"key":"2026092309101969000_16.9.e120552.35","doi-asserted-by":"crossref","DOI":"10.1093\/braincomms\/fcab301","article-title":"Phenotyping of multiple sclerosis lesions according to innate immune cell activation using 18 kDa translocator protein-PET","volume":"4","author":"Nylund","year":"2022","journal-title":"Brain Commun"},{"key":"2026092309101969000_16.9.e120552.36","doi-asserted-by":"crossref","unstructured":"Polvinen E , Matilainen M , Nylund M , et al . TSPO-Detectable Chronic Active Lesions Predict Disease Progression in Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm 2023;10. doi:10.1212\/NXI.0000000000200133","DOI":"10.1212\/NXI.0000000000200133"},{"key":"2026092309101969000_16.9.e120552.37","doi-asserted-by":"crossref","DOI":"10.1186\/1742-2094-9-232","article-title":"Evaluation of age-related changes in translocator protein (TSPO) in human brain using (11)C-[R]-PK11195 PET","volume":"9","author":"Kumar","year":"2012","journal-title":"J Neuroinflammation"},{"key":"2026092309101969000_16.9.e120552.38","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/s00259-021-05601-y","article-title":"Imaging translocator protein expression with positron emission tomography","volume":"49","author":"Wimberley","year":"2021","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2026092309101969000_16.9.e120552.39","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.08.058"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2026-120552","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:11:02Z","timestamp":1790179862000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2026-120552"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":39,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,23]]},"published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1136\/bmjopen-2026-120552"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2026-120552","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]}}}