Phytochemicals in MASLD: A Focused Review of Gut Microbiome-Linked Mechanisms

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a major global health burden, yet effective pharmacological options remain limited. Recent advances highlight the gut microbiome as a key modulator of liver metabolism, inflammation, and fibrosis, making it a promising therapeutic target. Among various non-pharmacologic strategies, phytochemicals have drawn growing attention for their ability to influence the gut-liver axis through natural, multitarget mechanisms. This mini-review summarizes preclinical and clinical evidence on phytochemicals that demonstrate metabolic benefits in MASLD, with a focus on their microbiome-mediated effects. To this end, we classify these mechanistic pathways into three major continuums: restoration of gut microbial composition (causation), modulation of signaling mediators, i.e., gut microbial metabolites (mediation), and the resulting functional outcomes derived from these causal links (outcome). While early pre-clinical data are encouraging, translation is challenged by issues such as mechanistic complexity, microbiome-dependent heterogeneity, and regulatory ambiguity. Future studies incorporating multi-omics analysis, mechanism-linked trial designs, and stratified patient populations will be critical to advancing phytochemicals as safe, effective, and personalized interventions for MASLD.