Targeting gut microbiota in liver disease: A pharmacological approach for hepatic encephalopathy and beyond

Abstract

The gut microbiota plays a pivotal role in the pathogenesis of liver diseases, particularly hepatic encephalopathy (HE), in which dysbiosis contributes to ammonia production, systemic inflammation, and neurocognitive dysfunction. Emerging evidence suggests that targeting the gut-liver axis through pharmacological and microbiota-based interventions can mitigate liver disease progression and HE severity. This review explored the latest therapeutic strategies aimed at modulating gut microbiota in liver disease, focusing on traditional approaches such as non-absorbable disaccharides (lactulose, lactitol), antibiotics (rifaximin), and probiotics as well as novel interventions, including postbiotics, synbiotics, and fecal microbiota transplantation. Additionally, bile acid modulators, short-chain fatty acid derivatives, and microbiome-targeted small molecules are being investigated for their potential to restore gut-liver homeostasis. We also discussed the implications of gut microbiota modulation in conditions beyond HE, such as metabolic dysfunction-associated steatotic liver disease and cirrhosis. By integrating gut microbiota-targeted therapies into liver disease management, we may develop more effective, personalized approaches to improve patient outcomes and reduce complications.

Keywords: Gut microbiota; Hepatic encephalopathy; Gut-liver axis; Probiotics; Fecal microbiota transplantation; Cirrhosis; Fatty liver

Core Tip: The gut microbiota is a key player in the progression of liver diseases, especially hepatic encephalopathy, by influencing ammonia levels, inflammation, and neurocognitive function. This review discussed current and emerging therapies that target the gut-liver axis, including non-absorbable disaccharides, antibiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation. Novel agents such as bile acid modulators and microbiome-targeted molecules were also explored. Modulating gut microbiota may not only alleviate hepatic encephalopathy but also benefit conditions like metabolic dysfunction-associated steatotic liver disease and cirrhosis, facilitating the way for more personalized and effective liver disease management strategies.