Depression in Diarrhea-Predominant IBS Patients: Exploring the Link Between Gut Barrier Dysfunction and Erythrocyte Polyunsaturated Fatty Acid Levels

<b>Background</b>: Patients with irritable bowel syndrome (IBS) often experience comorbid psychological conditions, notably depression and anxiety. Evidence suggests that these conditions are linked to gut barrier dysfunction, dysbiosis, and chronic inflammation. All these factors are central to IBS pathophysiology and mood disturbances. Polyunsaturated fatty acids (PUFAs) play crucial roles in modulating inflammation and depression. This study examined the associations among intestinal permeability, PUFA profiles, low-grade inflammation, and depression severity in IBS patients with diarrhea (IBS-D). <b>Methods</b>: Forty-three IBS-D patients (7 men, 36 women; 44.56 ± 1.52 years) were categorized into depressed (IBS-D(d+)) and non-depressed (IBS-D(d-)) groups according to scores on the depression subscale of the Symptom Checklist-90-Revised (SCL-90-R). Biomarkers of small intestinal permeability (s-IP) were assessed in urine and blood, alongside erythrocyte membrane PUFA composition, dysbiosis, and inflammation indices. <b>Results</b>: IBS-D (d+) patients exhibited elevated s-IP and altered PUFA metabolism compared to their IBS-D (d-) counterparts. Additionally, in the first group, omega-3 PUFA concentrations inversely correlated with s-IP biomarkers, while the omega-6/omega-3 ratio showed a positive correlation. Moreover, depression severity is significantly associated with s-IP markers and omega-3 PUFA levels. Lastly, IBS-D (d+) patients exhibited higher levels of dysbiosis and pro-inflammatory cytokines than IBS-D (d-) patients. <b>Conclusions</b>: These findings highlight the interplay between intestinal barrier integrity and PUFA metabolism in IBS-D patients with depression, suggesting that s-IP markers and erythrocyte PUFA profiles could represent novel therapeutic targets for managing depression in this population. This study was registered on ClinicalTrials.gov (NCT03423069), with a date of registration of 30 January 2018.