Ji Zhou, Bowen Zhu, Ziqian Bing, Tingting Wang, Yue Zhao
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging global health challenge with limited effective therapeutic options. The gut microbiota, at the interface of host metabolism and immunity, acts as a critical disease modifier via the gut-liver axis. This review goes beyond cataloging its associations and synthesizes how intrinsic and extrinsic factors sculpt a permissive microbial ecosystem. These factors likely converge to establish a state of "metabolic dysbiosis", fueling MASLD progression through three core mechanisms: compromised intestinal barrier integrity with immune activation, dysregulation of key microbial metabolite axes, and direct hepatic insult from gut-derived products. Next, we evaluate the translational landscape through a mechanism-informed precision framework, with an emphasis on how microbiome-based interventions could be aligned with non-invasive biomarkers increasingly used for MASLD risk stratification and treatment monitoring. By integrating evidence across scales, this review aims to frame a roadmap from microbiome correlations to causality-driven, personalized therapeutic strategies for MASLD.