The gut-lung axis in childhood asthma: from early-life programming to microbiome-informed precision medicine—a narrative review

The gut-lung axis links early-life microbial programming to long-term respiratory health, offering a pivotal framework for understanding childhood asthma pathogenesis. This review synthesizes current evidence on how disruptions in microbial-immune crosstalk during critical developmental windows shape asthma susceptibility. Perinatal determinants—including maternal diet, delivery mode, antibiotic exposure, and breastfeeding—establish gut microbial communities that educate the developing immune system. Distinguishing itself from recent reviews, this review offers three novel contributions: (i) an integrated multi-omics framework linking early-life microbial maturation trajectories to specific asthma endotypes; (ii) a systematic synthesis of the molecular mechanisms by which microbial metabolites—including short-chain fatty acids, tryptophan derivatives, and bile acids—orchestrate gut-lung immune crosstalk; and (iii) a clinically actionable precision medicine algorithm that translates multi-omics profiling into personalized risk prediction, endotype-driven therapy selection, and targeted preventive strategies. Dysbiosis, characterized by delayed microbial maturation and depletion of short-chain fatty acid-producing taxa, compromises epithelial barrier integrity and skews immune homeostasis toward pro-allergic type-2 responses. Microbial metabolites, particularly short-chain fatty acids (acetate, propionate, butyrate) and tryptophan derivatives (indole-3-lactic acid, indole-3-propionic acid), serve as key molecular mediators that regulate regulatory T cells differentiation, reinforce mucosal barriers, and modulate distal airway inflammation. Microbial signatures correlate with specific asthma endotypes, offering opportunities for patient stratification. We critically evaluate emerging microbiome-targeted interventions—including strain-specific probiotics, prebiotics, postbiotics, and fecal microbiota transplantation—highlighting both therapeutic promise and the need for rigorous, well-powered clinical trials. Integrating multi-omics microbial profiling with host genetics and clinical phenotyping holds potential for microbiome-informed precision medicine, enabling personalized risk prediction, endotype-driven therapy selection, and novel preventive strategies targeting the gut-lung axis from the earliest stages of life.