Serum zonulin measured by enzyme-linked immunosorbent assay may not be a reliable marker of small intestinal permeability in healthy adults

The association between intestinal permeability (IP) and body composition remains unclear. The gold standard differential sugar-absorption test is arduous to complete, with zonulin being increasingly used as an independent biomarker of IP. This pilot study aimed to explore the association between small IP, zonulin concentrations and body composition in healthy adults. The urinary lactulose-rhamnose ratio was used to measure small IP. Serum zonulin, lipopolysaccharide (LPS) and high-sensitivity C-reactive protein (hs-CRP) were analyzed in serum. Body composition was measured using dual-energy X-ray absorptiometry and anthropometric measurements were collected. In total, 34 participants were included (12 males, median age 28 years, body mass index 24kg/m2, waist circumference 77cm). No correlation was observed between the lactulose-rhamnose ratio and zonulin (r -0.016, p 0.929). The lactulose-rhamnose ratio displayed a strong positive correlation with LPS (n 22, r 0.536, p 0.018) but did not correlate with body composition measures. Conversely, zonulin displayed a moderate positive correlation with waist circumference (r 0.437, p 0.042) in female participants and hs-CRP (r 0.485, p 0.004) in all participants. These findings raise important considerations for the measurement of small IP, warranting exploration in larger powered studies that address the limitations of the present study.