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Review
. 2023 Apr 28;11(2):452-458.
doi: 10.14218/JCTH.2022.00089. Epub 2022 Aug 22.

Intestinal Barrier Function in the Pathogenesis of Nonalcoholic Fatty Liver Disease

Lu Liu  1 , Minyue Yin  1 , Jingwen Gao  1 , Chenyan Yu  1 , Jiaxi Lin  1 , Airong Wu  1 , Jinzhou Zhu  1 , Chunfang Xu  1 , Xiaolin Liu  1
Affiliations
Review

Intestinal Barrier Function in the Pathogenesis of Nonalcoholic Fatty Liver Disease

Lu Liu et al. J Clin Transl Hepatol. .

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The mechanisms involved in NAFLD onset are complicated and multifactorial. Recent literature has indicated that altered intestinal barrier function is related to the occurrence and progression of liver disease. The intestinal barrier is important for absorbing nutrients and electrolytes and for defending against toxins and antigens in the enteric environment. Major mechanisms by which the intestinal barrier influences the development of NAFLD involve the altered epithelial layer, decreased intracellular junction integrity, and increased intestinal barrier permeability. Increased intestinal permeability leads to luminal dysbiosis and allows the translocation of pathogenic bacteria and metabolites into the liver, inducing inflammation, immune response, and hepatocyte injury in NAFLD. Although research has been directed to NAFLD in recent decades, the pathophysiological changes in NAFLD initiation and progression are still not completely understood, and the therapeutic targets remain limited. A deeper understanding on the correlation between NAFLD pathogenesis and intestinal barrier regulation must be attained. Therefore, in this review, the components of the intestinal barrier and their respective functions and disruptions during the progression of NAFLD are discussed.

Keywords: Gut-liver axis; Intestinal barrier; Intestinal barrier permeability; Nonalcoholic fatty liver disease.

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Conflict of interest statement

The authors have no conflict of interests related to this publication.

Figures

Fig. 1
Fig. 1. Intestinal barrier components and the pathophysiological changes in NAFLD.
(A–D) The intestinal barrier is composed of a complex combination of mechanical (A), chemical (B), immunological (C) and microbial barriers (D). The mechanical barrier comprises the mucus layer, epithelial cells, intercellular tight junctions, and the lamina propria. The gut vascular barrier under the epithelium is composed of vascular endothelial cells, pericytes or fibroblast cells, and enteric glial cells. The chemical barrier includes gastric acid, mucus, bile and bile acids, mucopolysaccharides, digestive enzymes, lysozymes, antimicrobial peptides, and other molecules. The immunological barrier is composed of intestinal epithelial cells, mononuclear phagocytes, innate lymphoid cells, B and T lymphocytes and goblet cells. The microbial barrier includes bacteria, fungi, protozoa, archaea, and even viruses. Impaired intestinal epithelial cells, damaged intercellular junctions, and vascular barrier disruption lead to increased intestinal permeability. Imbalance of the chemical substances, especially bile acids enables invasion of the liver by micro-organisms and enzymes via the gut-liver axis. Immune cells and their immunoglobulins prevent pathogens in the gut from moving into the internal environment through innate and adaptive immunity. Dysbiosis, with increases of Proteobacteria, Enterobacteria, Escherichia, and Bacteroidetes and an decrease of Firmicutes, together with increases of harmful microbial metabolites, leads to the development of NAFLD. NAFLD, nonalcoholic fatty liver disease.
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