Search for new biomarkers using metabolomic analysis reflective of intestinal permeability in healthy Japanese participants

Abstract

Introduction: Improving intestinal barrier function may prevent the development of a variety of diseases. The lactulose-to-mannitol ratio (L/M) is the most widely used intestinal permeability test, but it lacks convenience and practicality.

Objectives: This study aims to validate the analysis of the relationship between L/M and metabolites in biological samples from two study populations, and to identify novel biomarkers that could increase sensitivity or simplify the detection of intestinal permeability.

Methods: After screening 115 people for this study, plasma, urine, and fecal samples were collected from eligible participants and L/M tests were conducted. Metabolomic analysis of samples was performed using HPLC-MS/MS.

Results: Data from 108 participants with available L/M test data were used for the analysis population. Participants were stratified into quartiles according to upper (positive) and lower (negative) quartile L/M test values. Candidate biomarkers of intestinal permeability was selected using comparison between two groups, partial least squares discriminant analysis (PLS-DA) and receiver operating characteristic (ROC) curves. Metabolites from plasma (n = 12), urine (n = 15), and feces (n = 36) were identified as candidate biomarkers of intestinal permeability. Data from another study comprising 149 participants was similarly analyzed, using the data from another study as the validation population. Several metabolites in plasma (n = 2), urine (n = 3), and feces (n = 3) were commonly detected in the analysis and validation populations. In feces, the predicted value using two metabolites resulted in an area under the curve of 0.853, surpassing that for a single metabolite.

Conclusions: Single or combined biological metabolites represented potential biomarkers for determining intestinal permeability. Evaluation of intestinal permeability via metabolomic analysis has utility in the early detection of diseases caused by an intestinal barrier breach.

Keywords: Biomarker; HPLC-MS/MS; Human; Intestinal permeability; Metabolites.