Elucidating the effect of the Mediterranean diet on fecal bile acids and their mediating role on biomarkers of intestinal barrier function: An exploratory analysis of a randomized controlled trial

Abstract

Background: Recent preclinical studies have suggested that gut microbiota-derived secondary bile acids affect intestinal barrier function. In this exploratory analysis, we studied the effect of the Mediterranean diet on fecal bile acid levels and their role in intestinal barrier regulation.

Methods: Data from women with impaired intestinal barrier function following the Mediterranean diet (intervention group, n = 33) or standard diet (control group, n = 35) were assessed in a randomized controlled trial (ClinicalTrials.gov: NCT02087592). Evaluations comprised baseline (BL), month 3 (V1), and month 12 (V2). Adherence to the Mediterranean diet was assessed using questionnaires, intestinal barrier function using validated biomarkers (plasma lipopolysaccharide binding protein (LBP) and fecal zonulin), and fecal bile acids using gas chromatography-mass spectrometry.

Results: As described before, the intervention group showed increased adherence to the Mediterranean diet and reduced plasma LBP and fecal zonulin levels over the entire observation period (BL-V1 and BL-V2, P < 0.01), whereas the control group did not. In the intervention group, the fecal levels of the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA) decreased, whereas the levels of the tertiary bile acid ursodeoxycholic acid increased (BL-V1 and BL-V2, P < 0.01). Multivariate analyses confirmed that the Mediterranean diet was inversely associated with DCA, LCA, LBP, and zonulin levels. Mediation analyses showed that decreases in DCA and LCA mediated the beneficial effects of the Mediterranean diet on LBP.

Conclusion: Consistent with previous pre-clinical studies, we found that the Mediterranean diet altered fecal secondary bile acid levels and that this alteration was associated with improved intestinal barrier function.

Keywords: Bile acids; Gut permeability; Intestinal barrier; Mediterranean diet; Microbiota.