ArticleFrontiers in physiology2026
Divergent intestinal barrier and neuroimmune responses to supervised exercise across fibromyalgia, irritable bowel syndrome, and their comorbidity phenotypes: a prospective interventional study.
Article in Frontiers in physiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 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). Methods: 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). Results: 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<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. Conclusions: 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.
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