{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T05:23:17Z","timestamp":1787289797909,"version":"build-2736575974"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fibromyalgia (FM) and irritable bowel syndrome (IBS) are overlapping functional somatic syndromes characterized by gut-brain axis dysregulation and low-grade systemic inflammation. We investigated whether a 16-week supervised combined exercise program is associated with phenotype-specific biomarker changes in patients with FM, IBS, or their comorbidity (FM+IBS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective, single-center, pre-post interventional study, 55 patients (FM, n=15; FM+IBS, n=21; IBS, n=19) completed a 16-week supervised program of aerobic, resistance, and flexibility training three times weekly. Pre- and post-intervention assessments included a panel of intestinal barrier, neuroimmune, and inflammatory biomarkers, together with the Global Physical Capacity Score (GPCS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the FM+IBS group, exercise was associated with significant reductions in urinary lactulose excretion (mean delta: -0.160%, p=0.001), L\/M ratio (mean delta: -0.011, p=0.026), serum zonulin (mean delta: -6.2 ng\/mL, p=0.016), fecal zonulin (mean delta: -65.9 ng\/mL, p=0.007), and urinary indoxyl sulfate (mean delta: -23.6 mg\/L, p=0.046), with post-intervention L\/M values falling below the 0.030 pathological threshold. In the IBS group, serum 5-HT increased (mean delta: +30.0 ng\/mL, p=0.028) and IBS-SSS decreased by 85.8 points (p&amp;lt;0.001), exceeding the minimally important difference; both findings were confirmed in a sensitivity analysis restricted to 14 female patients (5-HT: p=0.033; IBS-SSS: p=0.004). In the FM group, IL-6 increased (mean delta: +0.37 pg\/mL, p=0.013) and GPCS improved (p=0.047). BDNF, I-FABP, DAO, and LPS remained unchanged across all groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Sixteen weeks of combined exercise were associated with phenotype-specific biological patterns. FM+IBS patients showed reductions in barrier-related markers, supported by two independent assays (L\/M ratio and indoxyl sulfate), while IBS patients exhibited enhanced serotonergic signaling and symptom relief, both robust to sex-stratified sensitivity analysis. The isolated IL-6 increase in FM patients requires caution, since an acute myokine effect and a chronic inflammatory drift are both compatible with a single measurement taken 16 weeks apart. These exploratory findings, constrained by this proof-of-concept design, support phenotype-stratified randomized controlled trials with active comparators to validate and characterize these differential responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1912788","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T04:22:55Z","timestamp":1787286175000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Divergent intestinal barrier and neuroimmune responses to supervised exercise across fibromyalgia, irritable bowel syndrome, and their comorbidity phenotypes: a prospective interventional study"],"prefix":"10.3389","volume":"17","author":[{"given":"Antonella","family":"Bianco","sequence":"first","affiliation":[{"name":"Laboratory of Movement and Wellness, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d","place":["Castellana Grotte, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Russo","sequence":"additional","affiliation":[{"name":"Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d","place":["Castellana Grotte, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Prospero","sequence":"additional","affiliation":[{"name":"Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d","place":["Castellana Grotte, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetana","family":"Laselva","sequence":"additional","affiliation":[{"name":"Rheumatology Outpatient Clinic, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d","place":["Castellana Grotte, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Grasso","sequence":"additional","affiliation":[{"name":"Outpatient Pain Management Unit, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d","place":["Castellana Grotte, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"D\u2019Attoma","sequence":"additional","affiliation":[{"name":"Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d","place":["Castellana Grotte, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Verrelli","sequence":"additional","affiliation":[{"name":"Laboratory of Movement and Wellness, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d","place":["Castellana Grotte, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Ignazzi","sequence":"additional","affiliation":[{"name":"Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d","place":["Castellana Grotte, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Franco","sequence":"additional","affiliation":[{"name":"Laboratory of Movement and Wellness, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d","place":["Castellana Grotte, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Grazioli","sequence":"additional","affiliation":[{"name":"University of Rome \u201cForo Italico\u201d","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attilio","family":"Parisi","sequence":"additional","affiliation":[{"name":"University of Rome \u201cForo Italico\u201d","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Riezzo","sequence":"additional","affiliation":[{"name":"Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d","place":["Castellana Grotte, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1111\/apt.12194","article-title":"Serum I-FABP as marker for enterocyte damage in coeliac disease and its relation to villous atrophy and circulating autoantibodies","volume":"37","author":"Adriaanse","year":"2013","journal-title":"Aliment. 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