The Relationship between Low Serum Vitamin D Levels and Altered Intestinal Barrier Function in Patients with IBS Diarrhoea Undergoing a Long-Term Low-FODMAP Diet: Novel Observations from a Clinical Trial

Abstract

Decreased serum vitamin D (VD) levels have been associated with gastrointestinal (GI) disorders, including irritable bowel syndrome (IBS). VD can also modulate the intestinal barrier. Given the link between the GI barrier's alterations and diet, attention has aroused the positive effects of the Low FODMAP Diet (LFD) on IBS patients' symptom profile. We evaluated the GI symptoms and the urinary and circulating markers of GI barrier function, the markers of inflammation and intestinal dysbiosis in 36 IBS patients with predominant diarrhea (IBS-D) (5 men and 31 women, 43.1 ± 1.7 years) categorized for their circulating VD levels in low (L-VD) and normal (N-VD) (cutoff = 20 ng/mL). Evaluations were performed before and after 12 weeks of LFD. At the baseline, L-VD patients showed a significantly worse symptom profile and altered small intestinal permeability (s-IP) than N-VD. After LFD, a significant increase in the circulating VD levels in both the subgroups and a significant improvement of s-IP in L-VD patients occurred. Finally, VD levels negatively correlated with the symptom score and fecal zonulin. These data highlight the close relationship between VD and the intestinal barrier and support their involvement in IBS-D pathophysiology. Moreover, the potentially positive role of LFD in the management of IBS-D was confirmed.

Keywords: intestinal barrier; irritable bowel syndrome; low FODMAP diet; symptom profile; vitamin D.

Figure 1

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

Figure 2

VD levels in IBS-D patients as a whole group and categorized in L-VD and N-VD subgroups according to their low or normal vitamin D (VD) levels at baseline, before (pre) and after (post) 12 weeks of the low FODMAP diet. Data expressed as means ± SEM. Wilcoxon rank-sum test (solid line) was used to compare pre and post-treatment data. The Mann–Whitney test (dotted line) was applied in comparing the two subgroups before and at the end of the diet. Differences considered significant at p < 0.05. The red dotted line indicates the cutoff value.

Figure 3

Small intestinal permeability as evaluated by the sugar absorption test (panel (A) =% lactulose; panel (B) =% mannitol; panel (C) = La/Ma ratio; panel (D) =% sucrose) before (pre) and after (post) 12 weeks of low FODMAP diet in the IBS-D patients considered as a total group and categorized in L-VD and N-VD subgroups according to their low or normal VD levels at baseline. Data expressed as means ± SEM. Wilcoxon rank-sum test (solid line) was used to compare pre- and post-treatment data. The Mann–Whitney test (black dotted line) was applied in comparing the two subgroups before and at the end of the diet. Differences considered significant at p < 0.05. Red dotted line indicates the cutoff value of the La/Ma ratio (0.030).

Figure 4

Biomarkers of intestinal barrier function and integrity (panel (A) = fecal zonulin; panel (B) = serum zonulin, panel (C) = intestinal fatty acid-binding protein—I-FABP, and panel (D) = diamine oxidase—DAO) before (pre) and after (post) 12 weeks of low FODMAP diet in the IBS-D patients considered as a total group and categorized in L-VD and N-VD subgroups according to their low or normal VD levels at baseline. Data expressed as means ± SEM. Wilcoxon rank-sum test (solid line) was used to compare pre- and post-treatment data. The Mann–Whitney test (black dotted line) was applied in comparing the two subgroups before and at the end of the diet. Differences were considered significant at p < 0.05. Red dotted lines indicate the cutoff values for fecal and serum zonulin.

Figure 5

Indican (panel (A)) and skatole (panel (B)) levels as markers of dysbiosis before (pre) and after (post) 12 weeks of low FODMAP diet in the whole group of IBS-D patients and categorized in L-VD and N-VD subgroups according to their low or normal VD levels at baseline. Data expressed as means ± SEM. Wilcoxon rank-sum-test was used to compare pre- and post-treatment data. The Mann–Whitney test was applied in comparing the two subgroups before and at the end of the diet. Differences considered significant at p < 0.05. Red dotted lines indicate the cutoff value.