{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T23:11:13Z","timestamp":1778022673556,"version":"3.51.4"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"5-6","funder":[{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010203","name":"Walter Reed Army Institute of Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010203","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of the Army"},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Veteran Affairs CSR&D Research Career Scientist","award":["CX002074"],"award-info":[{"award-number":["CX002074"]}]},{"name":"Department of Veteran Affairs CSR&D Research Career Scientist","award":["CX001728"],"award-info":[{"award-number":["CX001728"]}]},{"name":"Department of Veteran Affairs CSR&D Research Career Scientist","award":["BX006069 & RX003818"],"award-info":[{"award-number":["BX006069 & RX003818"]}]},{"name":"James J. Peters VA Medical Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Military members are exposed in combat and training to recognized traumatic brain injury (TBI)-causing events and other sub-concussive events that result in physical, psychological, and physiological impacts. Studies by this team and others involving Service Members (SMs) engaged in tactical training operations with repeated exposure to low level blast (LLB) have shown associations with concussion-like symptomology as well as transient decrements in performance, blood-based neurotrauma biomarkers, and perturbations in epigenome and transcriptome profiles, as well as alterations in intestinal permeability (IP). The present study focused on SMs engaged in mortar fire tactical trainings, builds on our previous findings in breachers that identified associations between blast exposures and IP and neurotrauma symptoms following exposures to LLB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Self-report symptom data and blood specimens from 31 SMs were collected including 22 mortarmen who directly participated in tactical training operations and were exposed to LLB and 9 unexposed study controls. Symptom data and blood samples were collected at pre-, post, and follow-up time points, across 3 consecutive mortar fire training sessions. Blood samples were assessed across all sessions via enzyme-linked immunosorbent assay (ELISA) to measure levels of IP protein biomarkers (i.e., Zonulin, Lipopolysaccharide-Binding Protein (LBP), Claudin-3, Intestinal-Fatty Acid Biding Protein (I-FABP). Correlations between IP biomarker changes and magnitude of blast exposures in each training session were calculated and reported as effect sizes measured by Cohen\u2019s d using correlation to effect size conversion via R package effectsize. Impact of blast magnitude on IP biomarker changes across sessions were tested using a linear mixed effect model via R package lme4 and emmeans, with similar models used to investigate associations of IP biomarker changes following blast with physical and psychological symptoms or prior history of TBI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In mortarmen LLB exposure magnitudes were significantly associated with change in Intestinal-Fatty Acid Binding Protein (pre vs. post, P\u2009=\u2009.028) and Zonulin (pre vs. follow-up, P\u2009=\u2009.003) levels across training sessions. Associations with moderate to large effect sizes were observed between changes in LBP and CLDN3 levels and neurotrauma symptoms, including taking longer to think, dizziness, and concentration difficulties following exposures to LLB (Cohen\u2019s |d|\u2009&amp;gt;\u20090.5). Associations between TBI history and blast induced alterations in LBP and CLDN3 levels were identified with large effect sizes (|d|\u2009&amp;gt;\u20090.8).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The present study in mortarmen corroborates our prior findings showing that exposures to LLB can contribute to IP that is also associated with prior mild traumatic brain injury (mTBI) history, with concomitant decreases in self-reported cognitive functioning. These findings suggest a possible role of blast exposure in gut permeability and the importance of the gut-brain axis in blast injury, with significant clinical translational impact in how we target clinical symptoms associated with exposure to blast and long term sequalae. These results may lead to a paradigm shift in the manner by which the military can detect, mitigate, and treat blast-related sequelae.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/milmed\/usaf478","type":"journal-article","created":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T11:44:33Z","timestamp":1757763873000},"page":"e1077-e1085","source":"Crossref","is-referenced-by-count":0,"title":["Associations Between Blast Exposures and Intestinal Permeability and Neurotrauma Symptoms During Mortar Fire Military Tactical Training Operations"],"prefix":"10.1093","volume":"191","author":[{"given":"Zhaoyu","family":"Wang","sequence":"first","affiliation":[{"name":"General Medical Research, James J. Peters VA Medical Center , Bronx, NY 10468,","place":["United States"]},{"name":"Department of Neuroscience, Icahn School of Medicine at Mount Sinai , New York, NY 10029,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingkun","family":"Liu","sequence":"additional","affiliation":[{"name":"General Medical Research, James J. Peters VA Medical Center , Bronx, NY 10468,","place":["United States"]},{"name":"Department of Neuroscience, Icahn School of Medicine at Mount Sinai , New York, NY 10029,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Nemes","sequence":"additional","affiliation":[{"name":"Walter Reed Army Institute of Research , Silver Spring, MD 20910,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alis","family":"Kranfli","sequence":"additional","affiliation":[{"name":"Walter Reed Army Institute of Research , Silver Spring, MD 20910,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Molly","family":"Sullan","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs, Rocky Mountain Mental Illness, Research, Education and Clinical Care , Aurora, CO 80045,","place":["United States"]},{"name":"VA Brain Health Coordinating Center, Rocky Mountain Regional VA Medical Center , Aurora, CO 80045,","place":["United States"]},{"name":"Department of Physical Medicine & Rehabilitation, Anschutz Medical Campus, University of Colorado , Aurora, CO 80045,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Hoisington","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs, Rocky Mountain Mental Illness, Research, Education and Clinical Care , Aurora, CO 80045,","place":["United States"]},{"name":"VA Brain Health Coordinating Center, Rocky Mountain Regional VA Medical Center , Aurora, CO 80045,","place":["United States"]},{"name":"Department of Physical Medicine & Rehabilitation, Anschutz Medical Campus, University of Colorado , Aurora, CO 80045,","place":["United States"]},{"name":"Department of Systems Engineering and Management, Air Force Institute of Technology , Wright-Patterson Air Force Base, OH 45433,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa A","family":"Brenner","sequence":"additional","affiliation":[{"name":"VA Brain Health Coordinating Center, Rocky Mountain Regional VA Medical Center , Aurora, CO 80045,","place":["United States"]},{"name":"Department of Physical Medicine & Rehabilitation, Anschutz Medical Campus, University of Colorado , Aurora, CO 80045,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maciej","family":"Skotak","sequence":"additional","affiliation":[{"name":"Walter Reed Army Institute of Research , Silver Spring, MD 20910,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina R","family":"LaValle","sequence":"additional","affiliation":[{"name":"Walter Reed Army Institute of Research , Silver Spring, MD 20910,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongchao","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Icahn School of Medicine at Mount Sinai , New York, NY 10029,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter","family":"Carr","sequence":"additional","affiliation":[{"name":"Walter Reed Army Institute of Research , Silver Spring, MD 20910,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0920-6956","authenticated-orcid":false,"given":"Fatemeh","family":"Haghighi","sequence":"additional","affiliation":[{"name":"General Medical Research, James J. Peters VA Medical Center , Bronx, NY 10468,","place":["United States"]},{"name":"Department of Neuroscience, Icahn School of Medicine at Mount Sinai , New York, NY 10029,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"2026050517482008400_usaf478-B1","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1097\/HTR.0000000000000417","article-title":"Traumatic brain injury following military deployment: evaluation of diagnosis and cause of injury","volume":"34","author":"Regasa","year":"2019","journal-title":"J Head Trauma Rehabil"},{"key":"2026050517482008400_usaf478-B2","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1007\/s00193-017-0738-4","article-title":"Occupational overpressure exposure of breachers and military personnel","volume":"27","author":"Kamimori","year":"2017","journal-title":"Shock Waves"},{"key":"2026050517482008400_usaf478-B3","doi-asserted-by":"publisher","first-page":"619","DOI":"10.3389\/fneur.2020.00619","article-title":"Association of MOS-based blast exposure with medical outcomes","volume":"11","author":"Carr","year":"2020","journal-title":"Front Neurol"},{"key":"2026050517482008400_usaf478-B4","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1097\/HTR.0000000000000064","article-title":"Relation of repeated low-level blast exposure with symptomology similar to concussion","volume":"30","author":"Carr","year":"2015","journal-title":"J Head Trauma Rehabil"},{"key":"2026050517482008400_usaf478-B5","doi-asserted-by":"publisher","first-page":"e216445","DOI":"10.1001\/jamanetworkopen.2021.6445","article-title":"Neurotrauma biomarker levels and adverse symptoms among military and law enforcement personnel exposed to occupational overpressure without diagnosed traumatic brain injury","volume":"4","author":"Boutt\u00e9","year":"2021","journal-title":"JAMA Netw Open"},{"key":"2026050517482008400_usaf478-B6","doi-asserted-by":"publisher","first-page":"949","DOI":"10.3389\/fneur.2019.00949","article-title":"Neurocognitive performance deficits related to immediate and acute blast overpressure exposure","volume":"10","author":"LaValle","year":"2019","journal-title":"Front Neurol"},{"key":"2026050517482008400_usaf478-B7","doi-asserted-by":"publisher","first-page":"e771","DOI":"10.1093\/milmed\/usab394","article-title":"Repetitive low-level blast exposure and neurocognitive effects in Army Ranger Mortarmen","volume":"188","author":"Woodall","year":"2023","journal-title":"Mil Med"},{"key":"2026050517482008400_usaf478-B8","doi-asserted-by":"publisher","first-page":"8681","DOI":"10.1038\/s41598-018-26813-7","article-title":"Temporal and spatial effects of blast overpressure on blood-brain barrier permeability in traumatic brain injury","volume":"8","author":"Kuriakose","year":"2018","journal-title":"Sci Rep"},{"key":"2026050517482008400_usaf478-B9","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1097\/MCC.0b013e3280895d5c","article-title":"Neuroprotection in traumatic brain injury: a complex struggle against the biology of nature","volume":"13","author":"Schouten","year":"2007","journal-title":"Curr Opin Crit Care"},{"key":"2026050517482008400_usaf478-B10","year":"2014"},{"key":"2026050517482008400_usaf478-B11","doi-asserted-by":"publisher","first-page":"1179069519872213","DOI":"10.1177\/1179069519872213","article-title":"Blast-related traumatic brain injury: current concepts and research considerations","volume":"13","author":"Bryden","year":"2019","journal-title":"J Exp Neurosci"},{"key":"2026050517482008400_usaf478-B12","doi-asserted-by":"publisher","first-page":"404","DOI":"10.3389\/fncel.2014.00404","article-title":"Blood brain barrier dysfunction and delayed neurological deficits in mild traumatic brain injury induced by blast shock waves","volume":"8","author":"Shetty","year":"2014","journal-title":"Front Cell Neurosci"},{"key":"2026050517482008400_usaf478-B13","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1152\/physrev.1956.36.3.336","article-title":"Blast injury","volume":"36","author":"Clemedson","year":"1956","journal-title":"Physiol Rev"},{"key":"2026050517482008400_usaf478-B14","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1016\/s0196-0644(86)80940-4","article-title":"Primary blast injuries","volume":"15","author":"Phillips","year":"1986","journal-title":"Ann Emerg Med"},{"key":"2026050517482008400_usaf478-B15","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1067\/mem.2001.114906","article-title":"Explosions and blast injuries","volume":"37","author":"Wightman","year":"2001","journal-title":"Ann Emerg Med"},{"key":"2026050517482008400_usaf478-B16","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s12974-024-03118-3","article-title":"Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies","volume":"21","author":"El Baassiri","year":"2024","journal-title":"J Neuroinflammation"},{"key":"2026050517482008400_usaf478-B17","doi-asserted-by":"publisher","first-page":"3549","DOI":"10.3390\/ijms25063549","article-title":"Association of blast exposure in military breaching with intestinal permeability blood biomarkers associated with leaky gut","volume":"25","author":"Liu","year":"2024","journal-title":"Int J Mol Sci"},{"key":"2026050517482008400_usaf478-B18","doi-asserted-by":"publisher","first-page":"1976","DOI":"10.3390\/diagnostics13111976","article-title":"Fecal and circulating biomarkers for the non-invasive assessment of intestinal permeability","volume":"13","author":"Perez-Diaz-del-Campo","year":"2023","journal-title":"Diagnostics"},{"issue":"Pt 24","key":"2026050517482008400_usaf478-B19","doi-asserted-by":"publisher","first-page":"4435","DOI":"10.1242\/jcs.113.24.4435","article-title":"Human zonulin, a potential modulator of intestinal tight junctions","volume":"113","author":"Wang","year":"2000","journal-title":"J Cell Sci"},{"key":"2026050517482008400_usaf478-B20","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1002\/iub.175","article-title":"Regulation and roles for claudin-family tight junction proteins","volume":"61","author":"Findley","year":"2009","journal-title":"IUBMB Life"},{"key":"2026050517482008400_usaf478-B21","author":"Biometrics"},{"key":"2026050517482008400_usaf478-B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/00001199-199510030-00002","article-title":"Persistent postconcussion syndrome: the structure of subjective complaints after mild traumatic brain injury","volume":"10","author":"Cicerone","year":"1995","journal-title":"J Head Trauma Rehabil"},{"key":"2026050517482008400_usaf478-B23","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1007\/BF00868811","article-title":"The rivermead post concussion symptoms questionnaire: a measure of symptoms commonly experienced after head injury and its reliability","volume":"242","author":"King","year":"1995","journal-title":"J Neurol"},{"key":"2026050517482008400_usaf478-B24","doi-asserted-by":"publisher","first-page":"82","DOI":"10.3138\/jmvfh-2021-0122","article-title":"Blast effects on post-concussive and mental health outcomes: data from Canadian armed forces breachers and snipers","volume":"8","author":"Vartanian","year":"2022","journal-title":"J Mil Veteran Fam Health"},{"key":"2026050517482008400_usaf478-B25","doi-asserted-by":"publisher","first-page":"2815","DOI":"10.21105\/joss.02815","article-title":"Effectsize: estimation of effect size indices and standardized parameters","volume":"5","author":"Ben-Shachar","year":"2020","journal-title":"JOSS"},{"key":"2026050517482008400_usaf478-B26","doi-asserted-by":"publisher","first-page":"1589742","DOI":"10.3389\/fneur.2025.1589742","article-title":"Impact of prior exposures on biomarkers of blast during military tactical training","volume":"16","author":"Wang","year":"2025","journal-title":"Front Neurol"},{"key":"2026050517482008400_usaf478-B27","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1111\/apt.12269","article-title":"Combat-training increases intestinal permeability, immune activation and gastrointestinal symptoms in soldiers","volume":"37","author":"Li","year":"2013","journal-title":"Aliment Pharmacol Ther"},{"key":"2026050517482008400_usaf478-B28","doi-asserted-by":"publisher","first-page":"4734","DOI":"10.1021\/acs.jproteome.5b00603","article-title":"Gastrointestinal symptoms and altered intestinal permeability induced by combat training are associated with distinct metabotypic changes","volume":"14","author":"Phua","year":"2015","journal-title":"J Proteome Res"},{"key":"2026050517482008400_usaf478-B29","doi-asserted-by":"publisher","first-page":"G559","DOI":"10.1152\/ajpgi.00066.2017","article-title":"Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress","volume":"312","author":"Karl","year":"2017","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2026050517482008400_usaf478-B30","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.bbi.2022.02.002","article-title":"Stress and the gut-brain axis: cognitive performance, mood state, and biomarkers of blood-brain barrier and intestinal permeability following severe physical and psychological stress","volume":"101","author":"Varanoske","year":"2022","journal-title":"Brain Behav Immun"},{"key":"2026050517482008400_usaf478-B31","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.3389\/fmicb.2018.02013","article-title":"Effects of psychological, environmental and physical stressors on the gut microbiota","volume":"9","author":"Karl","year":"2018","journal-title":"Front Microbiol"},{"key":"2026050517482008400_usaf478-B32","doi-asserted-by":"publisher","first-page":"100346","DOI":"10.1016\/j.bbih.2021.100346","article-title":"Characterization of the gut microbiota among veterans with unique military-related exposures and high prevalence of chronic health conditions: a United States-Veteran microbiome project (US-VMP) study","volume":"18","author":"Stanislawski","year":"2021","journal-title":"Brain Behav Immun Health"},{"key":"2026050517482008400_usaf478-B33","doi-asserted-by":"publisher","first-page":"108217","DOI":"10.1016\/j.jnutbio.2019.108217","article-title":"A diet of US military food rations alters gut microbiota composition and does not increase intestinal permeability","volume":"72","author":"Karl","year":"2019","journal-title":"J Nutr Biochem"},{"key":"2026050517482008400_usaf478-B34","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1093\/milmed\/usad225","article-title":"Fiscal year 2018 National Defense Authorization Act, section 734, Weapon Systems Line of Inquiry: overview and blast overpressure tool\u2014a module for human body blast wave exposure for safer weapons training","volume":"188","author":"Spencer","year":"2023","journal-title":"Mil Med"},{"key":"2026050517482008400_usaf478-B35","doi-asserted-by":"crossref","first-page":"105562","DOI":"10.1016\/j.neubiorev.2024.105562","article-title":"Fermented foods: harnessing their potential to modulate the microbiota-gut-brain axis for mental health","volume":"158","author":"Balasubramanian","year":"2024","journal-title":"Neurosci Biobehav Rev"}],"container-title":["Military Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/milmed\/article-pdf\/191\/5-6\/e1077\/64517514\/usaf478.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/milmed\/article-pdf\/191\/5-6\/e1077\/64517514\/usaf478.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T22:19:41Z","timestamp":1778019581000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/milmed\/article\/191\/5-6\/e1077\/8275564"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,29]]},"references-count":35,"journal-issue":{"issue":"5-6","published-online":{"date-parts":[[2025,9,29]]},"published-print":{"date-parts":[[2026,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/milmed\/usaf478","relation":{},"ISSN":["0026-4075","1930-613X"],"issn-type":[{"value":"0026-4075","type":"print"},{"value":"1930-613X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,5]]},"published":{"date-parts":[[2025,9,29]]}}}