Relationship between Markers of Gut Barrier Function and Erythrocyte Membrane PUFAs in Diarrhea-Predominant IBS Patients Undergoing a Low-FODMAP Diet

Abstract

Many patients with irritable bowel syndrome (IBS) have a compromised intestinal barrier associated with low-grade inflammation. Polyunsaturated fatty acids (PUFAs) are potential mediators of inflammation: omega-6 PUFAs are pro-inflammatory, while omega-3 PUFAs are antioxidant and anti-inflammatory. Zonulin is a potential biomarker for small intestinal permeability (s-IP). This study investigated the relationship between PUFAs and gastrointestinal (GI) barrier integrity in IBS patients with predominant diarrhea (IBS-D). We evaluated GI barrier function indicators in the urine and bloodstream and erythrocyte membrane PUFA composition in 38 IBS-D patients (5 men, 33 women, 44.11 ± 1.64 years), categorized at baseline by fecal zonulin levels into high (≥107 ng/mL, H-FZ) and normal (<107 ng/mL N-FZ) groups. Evaluations were conducted prior to and following a 12-week diet low in FODMAPs (LFD). At baseline, H-FZ patients had s-IP significantly higher than the reference value, lower n-3 PUFAs levels, and higher n-6/n-3 PUFAs and arachidonic acid (AA) to eicosapentaenoic acid (EPA) ratios than N-FZ. After LFD, H-FZ patients showed significant increases in n-3 PUFAs levels; decreases in n-6 PUFAs, n-6/n-3 PUFAs and AA/EPA ratios; and improved s-IP. The n-6/n-3 PUFAs ratio positively correlated with fecal zonulin levels in all subjects. These findings highlight the relationship between PUFAs and the intestinal barrier, suggesting their role in IBS-D pathophysiology and confirming the positive effects of LFD in managing IBS-D.

Keywords: dietary carbohydrates; fatty acids; fatty acids unsaturated; fermentation FODMAPs; intestinal permeability; irritable bowel syndrome; omega-3; zonulin.

Figure 1

The flow of participants through this study. IBS-D = irritable bowel syndrome with prevalent diarrhea. F = females. M = males.

Figure 2

Zonulin levels in IBS-D patients. (A): Fecal zonulin levels. (B): Serum zonulin levels. Data are presented for measurements taken before (pre) and after (post) 12 weeks of a diet low in FODMAPs (LFD), categorized by baseline fecal zonulin levels as normal (N-FZ) or high (H-FZ). Data are indicated as the means ± SEM. The Wilcoxon rank-sum test (solid line) was performed to compare data pre- and post the diet. The Mann–Whitney test (black dotted line) was utilized to compare the two subgroups before and after the diet. Differences are assumed significant at p < 0.05. The red dotted line represents the cutoff value.

Figure 3

Gastrointestinal permeability assessed by the sugar absorption test. (A): % lactulose (Lac). (B) % mannitol (Man). (C): Lac/Man ratio. (D): % sucrose. Data are shown for measurements taken before (pre) and after (post) 12 weeks of a diet low in FODMAPs (LFD) in IBS-D patients, categorized by their baseline fecal zonulin levels as either normal (N-FZ) or high (H-FZ). Data are provided as the means ± SEM. The Wilcoxon rank-sum test (solid line) was used for comparison of data before and after diet. The Mann–Whitney test (black dotted line) compared the two subgroups before and after LFD. Significant differences were defined as p-values < 0.05. The red dotted line represents the cutoff value for the Lac/Man ratio (0.030).