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

Abstract

Background: 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). Methods: 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. Results: 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. Conclusions: 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.

Keywords: depression; inflammation; intestinal permeability; irritable bowel syndrome; omega-3 polyunsaturated fatty acids; polyunsaturated fatty acids.

Figure 1

The study flowchart. IBS-D: diarrhea-predominant irritable bowel syndrome; HCs: healthy controls. Red arrows indicate patients who dropped out of the study. Black arrows indicate patients who completed the study.

Figure 2

Urinary and serum markers of intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) patients categorized according to depression and healthy controls (HCs). Lac/Man (%Lac to %Man) ratio (A), fecal zonulin (B), and intestinal fatty acid-binding protein (I-FABP) (C). IBS-D(d+): IBS-D patients with depression (cutoff score ≥ 63); IBS-D(d−): IBS-D without depression (cutoff score < 63). Data are expressed as mean ± SEM and analyzed by the Kruskal–Wallis test with Dunn’s multiple comparison test. Bars not sharing the same letter are significantly different (p < 0.05).

Figure 3

Urinary indican (A) and serum lipopolysaccharide (LPS) (B) levels in diarrhea-predominant irritable bowel syndrome (IBS-D) patients categorized according to depression and healthy controls (HCs). IBS-D(d+): IBS-D patients with depression (cutoff score ≥ 63); IBS-D(d−): IBS-D without depression (cutoff score < 63). Data are expressed as mean ± SEM and analyzed by the Kruskal–Wallis test with Dunn’s multiple comparison test. Bars not sharing the same letter are significantly different (p < 0.05).

Figure 4

Mean percentage of red blood cell membrane n-6 (A), n-3 (B) and n-6/n-3 ratio (C) in diarrhea-predominant irritable bowel syndrome (IBS-D) patients categorized according to depression and healthy controls (HCs). IBS-D(d+): IBS-D patients with depression (cutoff score ≥ 63); IBS-D(d−): IBS-D without depression (cutoff score < 63); n-6: omega-6 polyunsaturated fatty acids, n-3: omega-3 polyunsaturated fatty acids. Data are expressed as mean ± SEM and analyzed by the Kruskal–Wallis test with Dunn’s multiple comparison test. Bars not sharing the same letter differ significantly (p < 0.05).