Interplay among IL1R1, gut microbiota, and bile acids in metabolic dysfunction-associated steatotic liver disease: a comprehensive review

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder characterized by hepatic steatosis associated with metabolic abnormalities. Recent research has shed light on the intricate interplay among interleukin-1 receptor 1 (IL1R1), gut microbiota, and bile acids in the pathogenesis of MASLD. This review aims to provide a comprehensive overview of the current understanding of the role of IL1R1, gut microbiota, and bile acids in MASLD, exploring their interrelationships and potential mechanisms. We summarize the evidence supporting the involvement of IL1R1 in inflammation, discuss the influence of gut microbiota on bile acid metabolism and its influence on liver health, and elucidate the bidirectional interactions among IL1R1 signaling, gut microbiota composition, and bile acid homeostasis in MASLD. Furthermore, we highlight emerging therapeutic strategies targeting these interrelated pathways for the management of MASLD. Interleukin-1 receptor 1 (IL1R1), gut microbiota, and bile acids play interconnected roles in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). IL1R1 signaling is involved in hepatic inflammation and injury in MASLD, and genetic variations in IL1R1 can influence disease susceptibility. Gut dysbiosis, characterized by alterations in gut microbiota composition, is associated with MASLD and can affect bile acid metabolism. Bile acids, in addition to their role in digestion, have effects on hepatic lipid metabolism, inflammation, and fibrosis in MASLD. Targeting IL1R1, modulating gut microbiota through interventions like probiotics and fecal microbiota transplantation (FMT), and modulating bile acid metabolism hold promise for therapeutic interventions in MASLD. Further research is needed to elucidate the precise mechanisms underlying these interactions to develop effective targeted interventions for MASLD management. image