Abstract Metabolic dysfunction–associated steatotic liver disease is associated with a growing global health burden with increasing prevalence in both adult and pediatric populations. Emerging evidence suggests that the origins of steatotic liver disease may trace back to early life, with the gut microbiota serving as a critical mediator in this developmental programming. This review synthesizes current knowledge on maternal-infant gut microbiota transmission and its role in shaping long-term liver health through the gut-liver axis. We examined key maternal factors, including delivery mode, feeding of breast milk, diet, metabolic status, and antibiotic exposure, that profoundly influence infant microbiota assembly. The critical window of microbiota establishment during the first 1000 days shapes intestinal barrier function, immune development, and metabolic pathways that persist into adulthood. Mechanistically, early dysbiosis contributes to metabolic dysfunction–associated steatotic liver disease pathogenesis through multiple interconnected pathways, including compromised intestinal barrier integrity facilitating endotoxemia, altered short-chain fatty acid production affecting energy metabolism and inflammation, disturbed bile acid signaling disrupting metabolic homeostasis, and epigenetic modifications potentially shaping long-term susceptibility. We critically evaluated emerging microbiota-targeted interventional strategies during pregnancy and infancy, including probiotics, human milk oligosaccharide supplementation, and synbiotic approaches, highlighting their potential for disease prevention. This review uniquely integrates concepts of developmental origins with detailed gut-liver axis mechanisms, emphasizing the maternal-infant microbial continuum as an underexplored but promising target for preventing metabolic liver disease. While significant research challenges remain, particularly in establishing causality and developing personalized interventions, modulation of the early gut microbiome offers an innovative preventive strategy against the rising tide of metabolic dysfunction–associated steatotic liver disease, potentially disrupting the intergenerational cycle of metabolic disease.
Meng et al. (Fri,) studied this question.