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However, the gastrointestinal toxicities can affect the quality of life and outcomes for many patients. The underlying local gut toxicity and systemic effects, including effects on mental health, are underexplored and poorly understood. Given emerging evidence of immunological communication across the gut\u2013brain axis, we investigated whether abdominal RT could induce distal immune alterations in the dural meninges and explored potential behavioural outcomes. Using a preclinical model of image-guided abdominal RT treatment, we induced a local myeloid-driven inflammatory response in the small intestine and colon. We observed significant systemic immune modulations in the peripheral blood and dural meninges, affecting a diverse range of immune cells. Whilst circulating immune changes largely resolved alongside recovery of intestinal inflammation, dural immune alterations were prolonged and dynamically shifted across time points. Depletion of the gut microbiota partially attenuated both local and systemic immune responses, particularly affecting RT-induced increases in neutrophil and monocyte populations, implicating microbiota-dependent mechanisms in mediating these effects. After recovery from acute intestinal toxicity, RT-treated mice displayed increased anxiety-like phenotypes without evidence of cognitive impairment. Collectively, these findings demonstrate that gut-targeted RT can drive systemic immunomodulatory effects that extend to the brain border tissues in a partially microbiota-dependent manner and can enhance anxiety-like behaviour in mice. This highlights the systemic immune consequences of RT beyond the targeted tissue site, and the potential importance of RT-mediated immune organ crosstalk in mediating therapy outcomes.<\/jats:p>","DOI":"10.1093\/discim\/kyag019","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:27:11Z","timestamp":1789673231000},"source":"Crossref","is-referenced-by-count":0,"title":["Gut irradiation and microbiota status modulate the meningeal immune landscape"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6923-5586","authenticated-orcid":false,"given":"Clara H","family":"Whiteley","sequence":"first","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester , Manchester ,","place":["UK"]},{"name":"Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Group, The University of Manchester , Manchester ,","place":["UK"]},{"name":"Manchester Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester , Manchester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2536-6012","authenticated-orcid":false,"given":"Urszula M","family":"Cytlak","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester , Manchester ,","place":["UK"]},{"name":"Manchester Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester , Manchester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isobelle L","family":"Blair","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester , Manchester ,","place":["UK"]},{"name":"Manchester Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester , Manchester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel J","family":"Ashman","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester , Manchester ,","place":["UK"]},{"name":"Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Group, The University of Manchester , Manchester ,","place":["UK"]},{"name":"Manchester Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester , Manchester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Parker","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester , Manchester ,","place":["UK"]},{"name":"Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Group, The University of Manchester , Manchester ,","place":["UK"]},{"name":"Manchester Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester , Manchester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy M","family":"Illidge","sequence":"additional","affiliation":[{"name":"Targeted Therapy Group, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester , Manchester ,","place":["UK"]},{"name":"Christie NHS Foundation Trust, Manchester Academic Health Science Centre , Manchester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas P","family":"Dyer","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester , Manchester ,","place":["UK"]},{"name":"Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Group, The University of Manchester , Manchester 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