Demonstration of Gut-Barrier Dysfunction in Early Stages of Non-alcoholic Fatty Liver Disease: A Proof-Of-Concept Study

Abstract

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TNFα is a key trigger of inflammation in diet-induced non-obese MASLD in mice

“…Moreover, in the study of Manka et al it was shown that the protective effects of the anti -TNFα treatment were associated with an improvement of hepatic steatosis in patients with Crohn's Disease [ 52 ]. Somewhat in contrast, in the present study, bacterial endotoxin levels suggested to be indicative of intestinal barrier dysfunction [ 53 ] were significantly higher in SFC-fed mice regardless of strain or treatment when compared with the respective controls. Supporting these findings, xylose permeation in small intestine was also similar between SFC-fed mice, regardless of strain.…”

Paracellular permeability and tight junction regulation in gut health and disease

“…Increased intestinal permeability is a risk factor for type 2 diabetes mellitus and is associated with obesity and nonalcoholic fatty liver disease 194,[197][198][199][200][201] Hyperglycaemia, high-fat diet, nonalcoholic fatty liver disease and obesity are associated with increased intestinal permeability [202][203][204][205][206][207][208] HIV/AIDS Increased permeability in HIV enteropathy; positive correlation with disease stage; increased in patients with untreated HIV infection 90,209,210 Increased intestinal permeability in simian immunodeficiency virus infection is associated with microbial translocation and systemic immune activation 211,212 Multiple organ dysfunction syndrome…”

Gut dysbiosis in nonalcoholic fatty liver disease: pathogenesis, diagnosis, and therapeutic implications

“…Growing investigations held the intestinal barrier dysfunction blame for inflaming the NAFLD progression ( Liu et al., 2021 ; Gupta et al., 2022 ; He et al., 2022 ; Leng et al., 2022 ; Kaushal et al., 2022 ; Yu et al., 2022 ). During the initiation and progression of NAFLD, large amounts of gut bacterial metabolites, bacterial components, and other hazards enter the liver through the portal vein due to the intestinal mucosal barrier disruption induced by various stimuli, with the increased intestinal permeability.…”