Gut–growth interactions across the life course: Implications for linear growth and pubertal development

Background: Normal growth from infancy through adolescence depends on the coordinated maturation of the gastrointestinal tract, gut microbiota, immune system, and endocrine axes. Increasing evidence indicates that the gut functions not only as a digestive organ but also as an immune and endocrine interface influence linear growth, growth velocity, and pubertal growth spurt. Disruptions in gut structure, microbial composition, or barrier integrity, particularly during sensitive developmental windows—may contribute to growth faltering and altered pubertal trajectories.

Objective: To synthesize evidence on age-related gut and intestinal changes from infancy to adulthood and their associations with growth outcomes, including linear growth, growth velocity, IGF-1 biology, and pubertal growth dynamics.

Methods: A structured narrative review of PubMed- and Scopus-indexed literature from the past 25 years was conducted, following PRISMA 2020 guidance. Included studies comprised randomized controlled trials, observational cohorts, mechanistic/translational studies, and high-quality reviews addressing gut development, microbiome maturation, enteropathy, endocrine interactions, and growth outcomes. Risk of bias was assessed using RoB 2 for randomized trials and ROBINS-I for non-randomized studies. Due to heterogeneity in designs and outcomes, findings were synthesized narratively and summarized in thematic tables.

Results: Five key evidence domains were identified. First, infancy is characterized by rapid gut structural growth, barrier maturation, enzymatic development, and immune training, all essential for supporting high early growth demands. Second, the gut microbiome undergoes staged maturation from infancy to childhood, with dysbiosis and chronic enteropathy, particularly in undernutrition—strongly associated with stunting and reduced IGF-1 activity. Third, mechanistic and translational studies identify the GH/IGF-1 axis as a central endocrine bridge linking gut microbial metabolites and inflammatory tone to skeletal growth. Fourth, puberty represents a second critical window of gut remodeling, with sex-specific microbiome shifts and possible bidirectional interactions between sex steroids and microbial metabolism that may influence pubertal timing and growth spurt tempo. Fifth, intervention evidence is strongest for microbiota-directed nutritional strategies in undernourished children, demonstrating improvements in biological recovery signals and, in selected studies, linear growth.

Conclusion: Gut maturation across the life course is closely aligned with growth biology. Dysbiosis, enteropathy, and gut-driven inflammation can suppress linear growth through metabolic and endocrine pathways, particularly via IGF-1 modulation. Puberty emerges as an additional sensitive window in which gut–hormone interactions may shape growth outcomes. Integrating gut health into growth assessment and management may improve diagnostic precision, therapeutic strategies, and prognostic counseling for children with growth disturbances.