Central precocious puberty (CPP) may be influenced by gut microbiota through changes in short-chain fatty acids (SCFAs), β-glucuronidase activity, and enterohepatic estrogen recycling. This narrative review integrates current evidence from human and animal studies exploring microbial contributions to pubertal timing. Across multiple cohorts, CPP is associated with loss of SCFA-producing commensals, such as Bacteroides, and increased abundance of taxa like Alistipes, Ruminococcus, and Lachnoclostridium. These microbial shifts are linked to altered SCFA profiles, diminished anti-inflammatory and neuroendocrine modulation, and enhanced reabsorption of estrogens via microbial β-glucuronidase activity. Experimental models support a causal connection: gut dysbiosis accelerates pubertal onset, whereas microbiota-targeted interventions can restore hormonal balance and delay activation of the HPG axis. While some overlap with obesity-associated microbiota exists, the endocrine-specific microbial changes observed in CPP suggest partially distinct mechanisms. Overall, the gut microbiota emerges as both a modulator and potential biomarker of early pubertal onset. Its integration into pediatric endocrine frameworks could improve early risk assessment and guide future interventions, though further validation through standardized, longitudinal, and diverse population studies is still required.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common chronic liver disorder in the pediatric population, closely paralleling the global rise in childhood obesity. Increasing evidence highlights the gut–liver axis as a key contributor to MASLD pathogenesis, with gut microbiota dysbiosis influencing hepatic steatosis through multiple interconnected mechanisms, including increased intestinal permeability, endotoxemia, altered bile acid metabolism, and modulation of host energy homeostasis. In children, the characterization of microbiota signatures associated with MASLD remains challenging due to heterogeneity across studies, age-related microbial dynamics, and methodological variability. This review synthesizes current evidence regarding the role of the gut microbiota in pediatric MASLD, focusing on pathogenetic pathways, reported microbial patterns, and microbiota-targeted therapeutic strategies, while incorporating relevant mechanistic evidence from adult studies where pediatric data remain limited. Although several taxa have been repeatedly associated with pediatric MASLD, findings are not yet sufficiently consistent for clinical application. Interventions such as probiotics, prebiotics, and dietary modulation show promising but still preliminary results, with limited high-quality pediatric trials available. A deeper mechanistic understanding and standardized study designs are needed to clarify causality and to support microbiota-based precision approaches in pediatric MASLD management.

Hypophosphatasia (HPP) encompasses a group of inherited metabolic bone disorders characterized by defective skeletal mineralization and variable clinical severity in childhood. Substantial allelic heterogeneity contributes to a broad pediatric clinical spectrum, ranging from life-threatening perinatal disease to milder phenotypes characterized by chronic functional impairment. Historically, management relied primarily on supportive interventions aimed at sustaining survival, without modifying the underlying enzymatic defect. The introduction of enzyme replacement therapy (ERT) with asfotase alfa has fundamentally altered the natural history of pediatric HPP by supplementing deficient alkaline phosphatase activity at sites of active mineralization, thereby improving skeletal integrity, enhancing survival in severe forms, and supporting long-term functional gains. This therapeutic shift has redirected clinical priorities from survival alone toward sustained functional development and health-related quality of life. Nevertheless, variability in disease expression and therapeutic response persists, reflecting both diagnostic timing and the molecular heterogeneity of ALPL variants, whose phenotypic consequences cannot be predicted with complete certainty. Growing recognition of the importance of early diagnosis has prompted exploratory efforts toward systematic identification strategies, including neonatal screening initiatives reported in selected populations, which suggest the potential for earlier therapeutic intervention during active skeletal development. Together, these considerations highlight pediatric HPP as a model of precision-oriented management in rare metabolic bone disease, where timely diagnosis and targeted enzyme replacement must be aligned with long-term, multidisciplinary care to optimize outcomes.