Clinical and microbial correlates of response to lifestyle intervention in pediatric metabolic dysfunction-associated steatotic liver disease

BACKGROUND: Lifestyle modifications are fundamental in managing metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to evaluate the effects of a 12-week lifestyle intervention on hepatic steatosis, liver function, and gut microbiota composition in pediatric MASLD patients, and to explore clinical and baseline microbial features associated with treatment response. RESULTS: A total of 40 patients were recruited, and 31 were included after applying exclusion criteria. After 12 weeks, significant reductions were observed in body weight, waist circumference, liver enzymes, and triglycerides. MRI-measured hepatic steatosis decreased from 27.1% to 20.8% (p < 0.05). Greater reductions in hepatic fat were associated with higher daily step counts and a higher proportion of dietary protein intake. Baseline gut microbial composition differed between clinical responder groups. Clostridium sensu stricto 1 was enriched in participants with significant weight loss, Faecalibacterium in those with ALT or GGT improvement, and Lachnospiraceae_ND3007_group in those with MRI-PDFF reduction, with baseline microbial profiles discriminating responders with AUC ≥ 0.75. CONCLUSIONS: A 12-week lifestyle intervention led to significant improvements in hepatic steatosis, metabolic parameters, and anthropometric measures in pediatric MASLD. Baseline gut microbial profiles differed between individuals with metabolic improvements, suggesting a potential association between pre-intervention microbiome composition and treatment response. TRIAL REGISTRATION: The Clinical Research Information Service of the Korea Center for Disease Control and Prevention, Number: KCT0010340.