The Role of Gut Microbiota in Childhood Short Stature: From Mechanistic Insights to Therapeutic Strategies

Short stature is a common pediatric endocrine–metabolic disorder characterized by impaired linear growth and increased risks of adverse health outcomes. Although previous reviews have summarized associations between gut microbiota and childhood health, few have focused on the mechanistic links among microbial composition, microbial-derived metabolites, endocrine regulation, and skeletal growth in short stature. This review provides an integrated framework exploring the potential interactions among gut microbiota composition, microbial-derived metabolites, endocrine regulation, and skeletal development in short stature. We summarize the clinical characteristics and epidemiological features of major short stature subtypes and discuss emerging evidence demonstrating the involvement of gut microbiota alterations and metabolite dysregulation in growth regulation. Particular attention is given to the bidirectional interactions between the gut microbiota and the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis, as well as the potential role of the gut–liver–bone axis in skeletal growth. Furthermore, this review integrates evidence from metabolomics studies, experimental animal models, and microbiota-targeted interventions to provide mechanistic insights into microbiota-mediated growth regulation. Dietary factors, physical activity, sleep, antibiotic exposure, probiotic interventions, and current clinical treatments are also discussed from the perspective of microbiota modulation. Despite increasing interest in microbiota-based strategies, clinical translation remains limited by insufficient functional validation, unclear causal relationships, and a lack of well-designed intervention trials. Future integration of functional microbiology, multi-omics approaches, and human-based validation platforms may facilitate the development of microbiome-based precision interventions for improving growth outcomes in children with short stature, particularly those with ISS.