Progressive microbial alterations in the human gut and lung across early life: implications for translational medicine

Early life represents a critical window for the establishment and maturation of the human microbiome. The sterile womb paradigm remains dominant in the field, but in utero microbial colonization is highly controversial due to challenges related to low-biomass contamination. After birth, the intestinal and pulmonary microbial communities undergo a programmed succession shaped by factors such as delivery mode, feeding practices, and environmental exposures, and they bidirectionally regulate host immune and metabolic homeostasis via the gut–lung axis. Dysbiosis during early life is closely associated with allergic diseases, metabolic disorders, and respiratory illnesses. This review summarizes the dynamic succession patterns of the intestinal and pulmonary microbiota during early life, analyzes the methodological origins of the ongoing controversy over in utero colonization, delineates the developmental characteristics of the pulmonary microbiome at distinct stages, and systematically discusses the translational potential, clinical risks, and ethical challenges of microbiome-targeted interventions. Collectively, this review aims to provide a theoretical reference for early-life health protection and disease prevention.