Development and functional adaptation of intestinal macrophages across the lifespan

Macrophages of the gastrointestinal system are central regulators of gut development, homeostasis and disease, yet their origin, functional diversification and life stage-specific roles remain incompletely integrated. This review aimed to provide a comprehensive synthesis of current knowledge on intestinal macrophage ontogeny, heterogeneity and function from prenatal development through adulthood and into the aging phase. We highlight emerging evidence defining embryonic and monocyte-derived macrophage populations, their specialised roles in tissue remodelling, immune regulation, vascular and neural support, and their dynamic turnover across the lifespan. The review also examines how disruption of key regulatory pathways, including those relating to interleukin 10 (IL10), transforming growth factor (TGFβ) and metabolic signalling, contributes to macrophage dysfunction in inflammatory bowel disease, as an example of a gastrointestinal disorder with macrophage involvement. By integrating findings from lineage-tracing, single-cell transcriptomics and functional studies, this review provides a unified framework for understanding intestinal macrophage biology across life stages. This review provides a strengthened understanding of intestinal macrophage biology and establishes a knowledge base for translational therapies that can modify macrophage function to target inflammatory disorders and maintain gut health.