Intestinal permeability in human nonalcoholic fatty liver disease: A systematic review and meta‐analysis

Abstract

Background The gut‐liver axis is considered to play a critical role in the development and progression of nonalcoholic fatty liver disease (NAFLD). The integrity of the epithelial barrier is crucial to protect the liver against the invasion of microbial products from the gut, although its exact role in NAFLD onset and progression is not clear. Methods We performed a systematic review and meta‐analysis of studies that addressed the intestinal permeability (IP) in association with NAFLD presence or severity as defined by the presence of nonalcoholic steatohepatitis (NASH) and the degree of steatosis, hepatic inflammation or fibrosis. A total of 14 studies were eligible for inclusion. Results Studies investigating IP in adult (n = 6) and paediatric (n = 8) NAFLD showed similar results. Thirteen of the included studies focussed on small IP, two studies on whole gut permeability and none on colonic permeability. In the pooled analysis, NAFLD patients showed an increased small intestinal permeability compared to healthy controls based on dual sugar tests (standardized mean difference 0.79, 95% CI 0.49‐1.08) and serum zonulin levels (standardized mean difference 1.04 ng/mL, 95% CI 0.40‐1.68). No clear difference in IP was observed between simple steatosis and NASH patients. Furthermore, whole gut and small intestinal permeability increased with the degree of hepatic steatosis in 4/4 studies, while no association with hepatic inflammation or fibrosis was observed. Conclusion Based on the limited number of studies available, IP appears to be increased in NAFLD patients compared to healthy controls and is associated with the degree of hepatic steatosis.

Nonalcoholic fatty liver disease or metabolic dysfunction‐associated fatty liver disease diagnoses and cardiovascular diseases: From epidemiology to drug approaches

“…An intact intestinal barrier is able to antagonize the translocation of bacterial products, while allowing active transport of nutrients across tight junctions. As reported in a recent meta‐analysis, intestinal permeability appears to be raised in NAFLD patients, being associated with the degree of hepatic steatosis 163 . In this complex scenario, a crucial role is played by the intestinal microbiota, playing a major role in NAFLD.…”

Supplementation of tributyrin, alone and in combination with fructooligosaccharide in high soybean meal diets for shrimp ( Litopenaeus vannamei ): Effects on growth, innate immunity and intestinal morphology

“…Also, the integrity of the mucosal barrier is essential to protect the liver against the invasion of microbial products from the intestine (De Munck et al, 2020). Generally, intestinal villus height (VH) and mucosal thickness (MT) are two essential indices and the intestinal absorptive capacity can be partly characterized by them (Manzanilla et al, 2004;Zhang et al, 2012;Zhang, Zhong, et al, 2020).…”

“…A healthy intestine is instrumental for absorbability and utilization of nutrients from diet and a main barrier function for animals to resist various stimuli of external environment (Zheng et al., 2018). Also, the integrity of the mucosal barrier is essential to protect the liver against the invasion of microbial products from the intestine (De Munck et al., 2020). Generally, intestinal villus height (VH) and mucosal thickness (MT) are two essential indices and the intestinal absorptive capacity can be partly characterized by them (Manzanilla et al., 2004; Zhang et al., 2012; Zhang, Zhong, et al, 2020).…”

Role and Mechanism of Gut Microbiota in Human Disease

“…The integrity of the gut barrier is critical to protect the liver from the invasion of intestinal microflora. A meta-analysis found that intestinal permeability in patients with NAFLD was higher than that in healthy controls and was associated with the degree of hepatic steatosis ( De Munck et al, 2020 ). Besides, the composition of gut microbes is different between NAFLD patients and healthy people.…”