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The gut-lung axis in childhood asthma: from early-life programming to microbiome-informed precision medicine-a
Miaojun Mo1, Linlin Chen2, Yi Wang3
1Department of Pediatrics, Wenling Maternal and Child Health Care Hospital, Wenling, Zhejiang, China.
Insights
Early-life gut microbiome development influences childhood asthma risk. Microbial metabolites and immune crosstalk are key, paving the way for precision medicine approaches to prevent and treat asthma.
Area of Science:
- Microbiome research
- Immunology
- Pediatric respiratory medicine
Background:
- The gut-lung axis connects early microbial exposures to long-term respiratory health, crucial for understanding childhood asthma.
- Perinatal factors like maternal diet, delivery mode, and antibiotic use shape the infant gut microbiome and immune system development.
- Disruptions in this early microbial-immune crosstalk increase susceptibility to childhood asthma.
Purpose of the Study:
- To synthesize evidence on how early-life microbial-immune interactions influence asthma susceptibility.
- To present an integrated multi-omics framework linking microbial maturation to asthma endotypes.
- To detail molecular mechanisms of microbial metabolites in gut-lung immune crosstalk and propose a precision medicine algorithm for asthma.
Main Methods:
- Systematic review of current evidence on the gut-lung axis in asthma pathogenesis.
- Multi-omics data integration to link microbial trajectories with asthma endotypes.
- Analysis of molecular mechanisms of microbial metabolites (SCFAs, tryptophan derivatives, bile acids) in immune regulation.
- Development of a precision medicine algorithm for asthma risk prediction and treatment.
Main Results:
- Dysbiosis, marked by delayed maturation and reduced short-chain fatty acid (SCFA)-producing bacteria, impairs barrier integrity and promotes allergic immune responses.
- Microbial metabolites, especially SCFAs and tryptophan derivatives, are critical mediators of gut-lung immune crosstalk, influencing T-cell differentiation and airway inflammation.
- Specific microbial signatures correlate with distinct asthma endotypes, enabling patient stratification.
- Emerging microbiome-targeted interventions show promise but require rigorous clinical validation.
Conclusions:
- Early-life microbial programming is pivotal for respiratory health and asthma development via the gut-lung axis.
- Microbial metabolites act as key signaling molecules regulating immune homeostasis and inflammation.
- Multi-omics profiling integrated with clinical data offers a path toward microbiome-informed precision medicine for personalized asthma prevention and treatment.
Abstract:
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.
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