Gut microbiota in patients with metabolic, dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent condition that can progress to fibrosis, steatohepatitis, and hepatocellular carcinoma. This review examines recent advances concerning the role of gut microbiota in MASLD and microbiota-focused interventions to positively impact disease outcome.

Dysbiotic microbiota and a compromised gut barrier facilitate the translocation of microbial-associated molecular patterns and harmful metabolites into the portal circulation and liver, where they exacerbate inflammatory and fibrogenic processes. Conversely, other bacterial metabolites have protective effects in the liver. Therefore, microbiota homeostasis is essential for maintaining liver health.

Levels of harmful bacterial metabolites including ethanol, NH 3 , trimethylamine-L-oxide, 2-oleylglycerol, and litocholic acid are often increased in patients with MASLD. Conversely, short-chain fatty acids, indole derivatives, histidine, and the acids taurodeoxycholic, 3-succinylcholic, and hyodeoxycholic are decreased. The main aim of current interventions/treatments is to reduce harmful metabolites and increase beneficial ones. These interventions include drugs (pemafibrate, metformin, obeticholic acid), natural compounds (silymarin, lupeol, dietary fiber, peptides), exogenous bacteria (probiotics, gut symbionts), special diets (Mediterranean diet, time-restricted feeding), as well as microbiota transplantation, and phage therapy. Most improve gut permeability, liver inflammation, and fibrosis through microbiota regulation, and are promising alternatives for MASLFD management. However, most results come from animal studies, while clinical trials in MASLD patients are lacking. Further research is therefore needed in this area.