Causal relationship between metabolic dysfunction-associated fatty liver disease and endotoxin biomarkers: A...

Although the relationship among lipopolysaccharides (LPS), LPS-binding proteins, and metabolic dysfunction-associated fatty liver disease (MAFLD) is widely studied, no conclusive evidence is available. In this study, we used mendelian randomization (MR) to study the causal relationship of LPS, LPS-binding proteins, and MAFLD. Using bidirectional two-sample MR method, we evaluated data from the genome wide association study; for this analysis, nonalcoholic fatty liver disease (NAFLD), liver fat percentage, and other metabolic syndromes were employed as outcomes. Furthermore, MR analysis mainly involved the inverse variance weighted method. Heterogeneity and pleiotropy tests were also conducted. LPS was found to have a causal relationship with NAFLD, obesity, high density lipoprotein cholesterol, and TG levels. Furthermore, TG levels and LBP had significant causal relationships. This study mainly concluded that LPS is a risk factor for NAFLD, obesity, high density lipoprotein cholesterol, and TG, corroborating it's the LPS role in MAFLD pathogenesis. Hence, optimizing the gut microbiota using proper diet, probiotics, or fecal microbiota transplantation may help to reduce inflammation and (IR), thereby improving lipid and glucose metabolism disorders. Although a causal relationship between TG and LBP was observed, further studies are required to determine a specific mechanism.