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Mode of delivery plays a significant role in shaping the initial microbiome development of newborns. Cesarean section often disrupts the natural microbial transfer that occurs during vaginal birth, potentially affecting immune maturation, vaccine responsiveness, and increasing the risk of gut-related disorders. This issue is particularly concerning in low- and middle-income countries (LMICs), where C-section rates continue to rise alongside challenges such as maternal and neonatal morbidity, mortality, and limited healthcare infrastructure. This article reviews global evidence on how birth mode influences the establishment of the early-life microbiome and outlines context-specific interventions such as personalized maternal-infant nutrition, improved antibiotic stewardship, optimized vaccine scheduling, enhanced childbirth education, and professional training. Integrating microbiome-informed birth practices into national maternal child health programs could help reduce unnecessary C-sections and promote equitable approaches to improve long-term health and well-being among cesarean-born infants.