Putative intestinal permeability markers do not correlate with cardiometabolic health and gut microbiota in humans, except for peptides recognized by a widely used zonulin ELISA kit

Abstract

Background and aims: Cardiometabolic diseases refer to a group of interrelated conditions, sharing metabolic dysfunctions like insulin resistance, obesity, dyslipidemia, and hypertension. The gut microbiota has been associated with CMD and related conditions. Alterations in the intestinal epithelium permeability triggered by chronic stress and diet could bridge gut microbiota with inflammation and CMD development. Here, we assessed the relationship between intestinal permeability and circulating SCFAs with cardiometabolic health status (CMHS) and gut microbiota in a sample of 116 Colombian adults.

Methods and results: Plasma levels of lipopolysaccharide-binding protein (LBP), intestinal fatty acid-binding protein (I-FABP), claudin-3, and purported zonulin peptides (PZP) were measured by ELISA, whereas plasmatic levels of acetate, propionate, butyrate, isobutyrate, and valerate were measured by gas chromatography/mass spectrometry. In addition, for further statistical analysis, we took data previously published by us on this cohort, including gut microbiota and multiple CMD risk factors that served to categorize subjects as cardiometabolically healthy or cardiometabolically abnormal. From univariate and multivariate statistical analyses, we found the levels of I-FABP, LBP, and PZP increased in the plasma of cardiometabolically abnormal individuals, although only PZP reached statistical significance.

Conclusions: Our results did not confirm the applicability of I-FABP, LBP, claudin-3, or SCFAs as biomarkers for associating intestinal permeability with the cardiometabolic health status in these subjects. On the other hand, the poorly characterized peptides detected with the ELISA kit branded as "zonulin" were inversely associated with cardiometabolic dysfunctions and gut microbiota. Further studies to confirm the true identity of these peptides are warranted.

Keywords: Biomarkers; Cardiometabolic dysfunctions; Dysbiosis; Gut microbiota; Gut permeability.