Intestinal Barrier Function in the Pathogenesis of Nonalcoholic Fatty Liver Disease

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.

Tea Polyphenol Epigallocatechin Gallate Protects Against Nonalcoholic Fatty Liver Disease and Associated Endotoxemia in Rats via Modulating Gut Microbiota Dysbiosis and Alleviating Intestinal Barrier Dysfunction and Related Inflammation

“…Whereas, the low concentration of intact EGCG detected in blood circulation due to its poor oral bioavailability in vivo made it hard to completely elucidate its pharmacological action mechanism. Intriguingly, recent advancements have shed light on indirect modulatory effects of EGCG on NAFLD via the gut-liver axis, including shifting the gut microbiota and its metabolites (e.g., LPS, SCFAs, and bile acids) and bolstering intestinal mucosal immunity. − Nevertheless, the mechanisms are still not fully elucidated because the effect of EGCG on intestinal barrier dysfunction is rarely mentioned, although a growing body of evidence has strongly supported that NAFLD development is closely related with altered gut microbiota metabolites, intestinal barrier disruption, and associated inflammation. , Therefore, the present study completely investigated the mechanisms underlying the hepatoprotective effect of EGCG using the HFD-induced NAFLD rat model and the LPS-induced Caco-2 cell injury model, focusing on the link among gut microbiota, including its metabolites, intestinal barrier function, and inflammation, which would further verify that the “gut microbiota-barrier-liver axis” was truly an alternative or primary therapeutic target of EGCG in improving NAFLD and related metabolic disorders.…”

“…26−28 Nevertheless, the mechanisms are still not fully elucidated because the effect of EGCG on intestinal barrier dysfunction is rarely mentioned, although a growing body of evidence has strongly supported that NAFLD development is closely related with altered gut microbiota metabolites, intestinal barrier disruption, and associated inflammation. 29,30 Therefore, the present study completely investigated the mechanisms underlying the hepatoprotective effect of EGCG using the HFD-induced NAFLD rat model and the LPSinduced Caco-2 cell injury model, focusing on the link among gut microbiota, including its metabolites, intestinal barrier function, and inflammation, which would further verify that the "gut microbiota-barrier-liver axis" was truly an alternative or primary therapeutic target of EGCG in improving NAFLD and related metabolic disorders.…”

Breaking the barriers: the role of gut homeostasis in Metabolic-Associated Steatotic Liver Disease (MASLD)

“…When alterations occur in the intestinal barrier function, it leads to increased intestinal permeability, which significantly contributes to the initiation and progression of intra and extrahepatic damage in MASLD. 96 , 97 MASLD is linked to gut barrier disruption, changes in TJs, rise in intestinal permeability and dysbiosis.…”

“…Loss of mucus and chemical substances in the gut barrier can lead to bacterial overgrowth in the GI tract, disrupting gut homeostasis and permeability. 96 …”

Co-Housing and Fecal Microbiota Transplantation: Technical Support for TCM Herbal Treatment of Extra-Intestinal Diseases Based on Gut Microbial Ecosystem Remodeling

“…A compromised intestinal barrier contributes to the disruption of intestinal integrity and immune homeostasis, ultimately affecting extra-intestinal diseases. [10][11][12] Given the impact of GME on susceptibility to extra-intestinal diseases, its utilization for therapeutic purposes may be promising. Previous studies have found that Traditional Chinese Medicine herbs (TCMs) have a close interaction with the GME.…”