Mechanisms of flavonoid-mediated amelioration of MASLD: flavonoids, their metabolites or impact on gut microbes?

Metabolic syndrome (MetS), characterized by symptoms like hyperlipidemia, abdominal obesity, and insulin resistance, is closely associated with metabolic dysfunction-associated steatotic liver disease (MASLD), an established disease burden worldwide. Health-promoting, side-effect-free preventative, and treatment strategies for MetS are required. Flavonoids, which are active phytochemicals easily obtained from dietary sources, have been shown in animal and population studies to improve lipid metabolism disorders and offer protective support against MASLD. However, it remains unclear which among flavonoids, their metabolites, or indirect mechanisms such as impact on gut microbiota most significantly ameliorates MASLD. This review first explores the diverse mechanisms through which flavonoids attenuate the onset and progression of MASLD. It then summarizes the flavonoid metabolites that have enhanced MASLD protection. Additionally, certain flavonoids can mitigate MASLD by reshaping the specific or entire gut microbiome. Finally, the review outlines the potential for developing prebiotic-probiotic systems with flavonoids and discusses potential directions for identifying causal relationship between flavonoids and MASLD amelioration.