Core Insights - Metabolic dysfunction-associated fatty liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is increasingly recognized as a global health crisis, with potential progression to severe liver conditions [3] - Currently, only one drug, Remetiro, is approved specifically for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), highlighting the urgent need for alternative strategies, with prebiotics emerging as a promising candidate [3] Research Findings - A study published in Cell Metabolism revealed that individual variability in gut microbiome mediates the efficacy of resistant starch (RS) on MASLD, indicating that different baseline gut microbiomes can drive variations in intervention responses [4] - The research team conducted a randomized, placebo-controlled clinical trial showing that RS, a natural prebiotic, has therapeutic effects on MASLD, although 30% of participants exhibited limited benefits, a finding corroborated in a multicenter clinical trial [6] - Multi-omics analysis and fecal microbiota transplantation (FMT) indicated that baseline gut microbiome is a major determinant of treatment response, with Prevotella inhibiting the degradation of RS, leading to low response rates [7] - Bifidobacterium pseudocatenulatum was isolated from the cohort, which can restore RS degradation and improve the response to RS inhibited by Prevotella [7] - A predictive model integrating baseline microbiome and clinical characteristics was developed, achieving an AUC of 0.74 - 0.87 for personalized intervention [8] Key Findings - Approximately one-third of MASLD participants showed poor response to RS intervention [11] - Prevotella mediates low response to RS by inhibiting RS-degrading bacteria [11] - Bifidobacterium pseudocatenulatum enhances the efficacy of RS [11] - A machine learning model based on baseline gut microbiome characteristics can predict responses to RS treatment [11] - The study suggests that gut microbiome determines the heterogeneity of RS treatment for MASLD, offering a potential for microbiome-guided precision therapy [12]