{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:45:01Z","timestamp":1792446301624,"version":"4.5.0"},"reference-count":135,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Traumatic brain injury (TBI) remains a major global health problem, contributing significantly to morbidity and mortality worldwide. Despite advances in understanding its complex pathophysiology, current therapeutic strategies are insufficient in addressing the long-term cognitive, emotional, and neurological impairments. While the primary mechanical injury is immediate and unavoidable, the secondary phase involves a cascade of biological processes leading to neuroinflammation, blood\u2013brain barrier (BBB) disruption, and systemic immune activation. The heterogeneity of patient responses underscores the urgent need for reliable biomarkers and targeted interventions. Emerging evidence highlights the gut\u2013brain axis as a critical modulator of the secondary phase, with microbiota-derived extracellular vesicles (MEVs) representing a promising avenue for both diagnosis and therapy. MEVs can cross the intestinal barrier and BBB, carrying biomolecules that influence neuronal survival, synaptic plasticity, and inflammatory signaling. These properties make MEVs promising biomarkers for early detection, severity classification, and prognosis in TBI, while also offering therapeutic potential through modulation of neuroinflammation and promotion of neural repair. MEV-based strategies could enable tailored interventions based on the individual\u2019s microbiome profile, immune status, and injury characteristics. The integration of multi-omics with artificial intelligence is expected to fully unlock the diagnostic and therapeutic potential of MEVs. These approaches can identify molecular subtypes, predict outcomes, and facilitate real-time clinical decision-making. By bridging microbiology, neuroscience, and precision medicine, MEVs hold transformative potential to advance TBI diagnosis, monitoring, and treatment. This review also identifies key research gaps and proposes future directions for MEVs in precision diagnostics and gut microbiota-based therapeutics in neurotrauma care.<\/jats:p>","DOI":"10.3390\/biom15101398","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T07:58:13Z","timestamp":1759305493000},"page":"1398","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Microbiota-Derived Extracellular Vesicles as Potential Mediators of Gut\u2013Brain Communication in Traumatic Brain Injury: Mechanisms, Biomarkers, and Therapeutic Implications"],"prefix":"10.3390","volume":"15","author":[{"given":"Tarek","family":"Benameur","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1195-9976","authenticated-orcid":false,"given":"Abeir","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hind","family":"Toufig","sequence":"additional","affiliation":[{"name":"Department of Surgery, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5457-1069","authenticated-orcid":false,"given":"Maria Antonietta","family":"Panaro","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari, I-70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2399-3781","authenticated-orcid":false,"given":"Francesca Martina","family":"Filannino","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, I-71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7526-6968","authenticated-orcid":false,"given":"Chiara","family":"Porro","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, I-71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.pneurobio.2017.03.005","article-title":"The nature of early astroglial protection\u2014Fast activation and signaling","volume":"153","author":"Kardos","year":"2017","journal-title":"Prog. 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