Exploring the Link between Leaky-Gut-Related Markers and Metabolic Health in a Large Dutch Adult Population.

Hiroyuki Hoshiko,Nicole J W De Wit,Els Oosterink,Renata M C Ariens,Jurriaan J Mes,Edith J M Feskens

doi:10.3390/metabo11120877

Hiroyuki Hoshiko, Nicole J W De Wit + Show 4 more

Open Access

https://doi.org/10.3390/metabo11120877

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Abstract

A leaky gut can trigger chronic inflammation and poses a primary risk for metabolic diseases. This study established a relationship between intestinal integrity (leaky gut) and metabolic health in a general population. Leaky-gut markers (LGMs) were studied in a large population of Dutch adults with a broad spectrum of metabolic health. This study enrolled 500 individuals selected within the NQplus cohort study (n = 2048) by stratified randomization, based on waist circumference, fasting glucose, and high-density lipoprotein (HDL) cholesterol to obtain a representative and balanced population in terms of metabolic health parameters, sex (male/female), and age (<54/≥54 years). LGMs—zonulin, lipopolysaccharide-binding protein (LBP), and soluble CD14 (sCD14)—were measured in EDTA plasma or serum. Zonulin was most strongly associated with metabolic health. Zonulin and LBP were most strongly associated with the inflammatory marker C-reactive protein (CRP). The quartile analysis for zonulin and LBP showed that most metabolic health parameters and CRP levels increased from Q1 to Q4, with significant differences between quartiles, except for markers related to glucose homeostasis (glucose and glycated hemoglobin A1c (HbA1c)). Associations between LGMs and metabolic health parameters in this large Dutch adult population indicate that LGMs are valuable markers for identifying people at risk of a leaky gut and subsequent chronic inflammation linked to metabolic disorders.

Highlights

Obesity, especially when characterized by a high waist circumference [1], is primarily linked to an unhealthy metabolic profile in humans [2]
We evaluated the application of zonulin, as it is associated with intestinal permeability, and lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14) as biomarkers for endotoxin-related translocation in a larger cohort of the adult Dutch population with a broad spectrum of metabolic parameters
Five hundred individuals were selected within the NQplus cohort study by stratified randomization for waist circumference, fasting glucose, and high-density lipoprotein (HDL) cholesterol to obtain a large adult population with a broad range in metabolic health

Summary

Introduction

Especially when characterized by a high waist circumference [1], is primarily linked to an unhealthy metabolic profile in humans [2]. Obesity is associated with chronic inflammation in the adipose tissue, which can lead to metabolic dysfunction [3]. A range of other factors may contribute to chronic inflammation, such as a leaky gut [4]. Recent hypotheses have linked a leaky gut to chronic inflammation due to the translocation of microbiome-derived lipopolysaccharide (LPS) into the bloodstream, possibly leading to metabolic endotoxemia. This LPS translocation may trigger inflammatory activation, eliciting a chronic low-grade pro-inflammatory and pro-oxidative stress status associated with chronic metabolic diseases linked to metabolic syndrome [5]. LPS in the blood binds to a lipopolysaccharide-binding protein (LBP), passes to sCD14, and subsequently transfers to myeloid differentiation factor 2 (MD2) and toll-like receptor

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