Gut microbiome and metabolic dysfunction-associated steatotic liver disease: Pathogenic role and potential for therapeutics

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a burdensome condition that has become a relevant cause of chronic liver disease globally. It is characterized by at least 5 % of intrahepatic fat and one or more cardiometabolic conditions in individuals who do not consume excessive amounts of alcohol [1].

The incidence of MASLD has grown along with the prevalence of overweight and obesity in both pediatric and adult populations, mainly in developed countries. The prevalence of MASLD in obese patients ranges from 40 to 70 % [2], in the general population it is approximately 25 %, and although minor, it may be also present lean individuals [3].

The progression of MASLD can lead to various outcomes, from simple steatosis to Metabolic Associated-Dysfunction Steatohepatitis (MASH) [1] which is an inflammatory condition characterized by liver fibrosis and hepatocellular ballooning, with potential progression to cirrhosis and hepatocellular carcinoma [4]. The development of these last two conditions is the strongest predictor of mortality in patients with MASLD, which is also linked to cardiovascular complications [5,6].

Since MASLD is closely related to metabolic syndrome, its pathophysiology includes obesity, inflammation, hypertriglyceridemia, hypertension, decreased high-density lipoprotein cholesterol levels, and elevated fasting plasma glucose levels [7]. Both metabolic syndrome and MASLD are strongly associated with lifestyle factors, and an altered gut-liver axis has emerged as a crucial factor in both the development and treatment of MASLD [8].

In this review article we aim unraveling the relationships between gut microbiome and MASLD, from pathogenesis to potential therapeutic applications.

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