Himalaya Livline | Vol 6 | No. 4 | May–Aug 2023 | 3 junctions that are crucial for preserving the integrity of the intestinal barrier. An impaired intestinal barrier function—also known as the leaky gut—is considered as a hallmark of dysbiosis in patients with NAFLD. Impaired gut permeability due to dysbiosis results in increased gut-derived toxins in the systemic circulation, which in turn contributes to the development of the chronic low-grade inflammation state observed in patients with NAFLD. Endotoxins and inflammation A tandem increase in the population of anaerobic gram-negative bacilli and the number of endotoxins impairs the intestinal barrier. An impaired intestinal barrier can overload the liver with endotoxins such as lipopolysaccharides and can cause loss of liver tolerance and establish a proinflammatory environment. The inflammatory state induced by endotoxins is also strongly linked to the immune response mediated by pattern recognition receptors and nucleotidebinding and oligomerization domainlike receptors. Further, inflammasomes also play a key role in the activation of lipid peroxidation and the production of reactive oxygen species, thereby contributing to gut microbiome dysbiosis and the advancement of NAFLD. Metabolites produced by the gut microbiome The metabolites in the gut can originate either from the microbiome itself, through microbial metabolism of food substrates, or by the alteration of bile acids. These metabolites that include endogenous ethanol, choline, and short-chain fatty acids can negatively affect the immune response and homeostasis, host energy metabolism, and mucosal integrity maintenance. Thus, it can be understood that the gut microbial health is important beyond localized gastrointestinal disorders and can influence systemic alterations. The rising prevalence of NAFLD is largely due to excessive calorie consumption, food additives and toxins, and antibiotic use, and decreased physical activity. Enhancement of the gut–liver axis through probiotics along with certain advantageous microbial products (such as baker’s yeast, kefir, and mushroom) can confer protection to the liver from the pathogenic constituents of the intestine. Further, advancing research about the gut–liver axis can contribute to the development of microbiota-based diagnostic, prognostic, and therapeutic tools for the treatment of NAFLD and other liver diseases. Sources: Pezzino S, et al. Biology. 2022;11(11):1622. Kaur KK, et al. J Hepatol Gastroint Dis. 2022;8(5):1000216. Summary • Gut dysbiosis serves as an important determinant for the development and progression of NAFLD. • An impaired intestinal barrier function—also known as the leaky gut—is considered as a hallmark of dysbiosis in patients with NAFLD. • Inflammasomes also play a key role in the activation of lipid peroxidation and the production of reactive oxygen species, thereby contributing to gut microbiome dysbiosis and the advancement of NAFLD. • Gut microbial health is important beyond localized gastrointestinal disorders and can influence systemic alterations.
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