Elevated Depressive Symptoms Shape Gut Barrier Integrity, LPS Translocation, and PUFA Composition in IBS-D: Evidence...

Introduction: Alterations of the microbiota-gut-brain axis, including increased intestinal permeability (IP), changes in microbial activity, and immune activation, are central to the pathophysiology of irritable bowel syndrome with diarrhea (IBS-D). The low-fermentable oligo-di-monosaccharides and polyols (FODMAP) diet (LFD) is an established therapy for IBS, yet its systemic effects, particularly in patients with elevated depressive symptoms, remain incompletely characterized. Methods: This single-arm pre-post study investigated associations between depressive symptom severity and markers of small IP (s-IP), endotoxin exposure, inflammation, and erythrocyte membrane polyunsaturated fatty acid (PUFA) composition in 43 IBS-D patients undergoing a 12-week personalized LFD. Patients were classified using the Symptom Checklist-90-Revised depression subscale into those with (d+, n = 23) and without (d-, n = 20) clinically elevated depressive symptoms. Results: At baseline, d+ patients exhibited higher s-IP, circulating lipopolysaccharide levels, inflammatory markers, and a more pro-inflammatory PUFA profile. Following LFD, significant improvements in symptoms and several biological parameters were observed in the overall cohort. Greater absolute changes in d+ patients were consistent with their higher baseline values rather than indicating differential responsiveness. Baseline depressive symptoms were not significantly associated with the magnitude of post-intervention changes in IP or inflammatory markers. Conclusions: These findings suggest that elevated depressive symptoms identify an IBS-D subgroup characterized by greater baseline biological burden. Results should be interpreted as associative given the single-arm design, absence of a control group, and the concurrent reduction in body weight, which may have influenced the observed changes. Randomized controlled studies are needed to clarify the role of dietary interventions in modulating gut-brain axis-related pathways in IBS-D.