Front Immunol. 2026 Sep 2;17:1902053. doi: 10.3389/fimmu.2026.1902053. eCollection 2026.

ABSTRACT

Childhood asthma is a highly heterogeneous chronic respiratory disease, and its onset and progression are intricately linked to genetic susceptibility, environmental exposure, immune development, and the establishment of the early-life microbiome. In recent years, studies on the gut and respiratory microbiomes have suggested that the composition, metabolic functions, and interactions of microbial communities with the host immune system may be involved in the formation of asthma susceptibility, shaping of inflammatory phenotypes, and disease progression in children. The gut-lung axis, as an important pathway connecting gut microbiome, respiratory immunity, and systemic inflammatory responses, provides a new perspective for understanding the early mechanisms of childhood asthma. This article reviews the characteristics of the respiratory and gut microbiomes associated with childhood asthma, with a focus on the roles of the gut-lung axis, microbial metabolites, mucosal immune regulation, and environmental exposure. It also evaluates the research progress of probiotics, prebiotics, nutritional interventions, and novel microecological therapies. Additionally, the potential of microbial maturity, microbial metabolites, and immunophenotypes as biomarkers for risk prediction, phenotype stratification, and treatment response is analyzed. Furthermore, the role of multi-omics integration in supporting the identification of responsive populations, matching of intervention strategies, and dynamic monitoring of efficacy is discussed. Current evidence suggests that the microbiome offers promising targets for risk assessment and precision prevention of childhood asthma. However, relevant research still faces challenges such as ambiguous causality, high cohort heterogeneity, limited reproducibility of candidate biomarkers, inconsistent intervention outcomes, and insufficient evidence of long-term safety. At present, most biomarkers and multi-omics models remain in the stage of association discovery, lacking unified thresholds, cross-cohort validation, and biomarker-guided randomized controlled trials in children. Therefore, they cannot be routinely used for patient stratification or intervention selection. Future efforts should rely on standardized longitudinal birth cohorts, multi-omics integration, external validation, and high-quality clinical trials to clarify the incremental value of microbiome biomarkers over traditional clinical indicators and their clinical utility in the individualized management of childhood asthma.

PMID:42751182 | PMC:PMC13580037 | DOI:10.3389/fimmu.2026.1902053

Front Immunol. 2026 Aug 21;17:1878054. doi: 10.3389/fimmu.2026.1878054. eCollection 2026.

ABSTRACT

Viral burden or pathogen identity alone cannot adequately explain the progression of severe viral pneumonia from a compartmentalized respiratory infection to acute respiratory distress syndrome, multi-organ failure, and death. Maladaptive immunity, endothelial damage, and coagulation dysregulation are all functionally integrated in a host-driven pathological mechanism that mediates disease escalation. Systemic microvascular damage and pulmonary inflammation are linked by immune-endothelial-coagulation interaction. This review investigates the ways in which immunothrombosis and microcirculatory dysfunction are propagated by defective antiviral immunity, alveolar-capillary barrier failure, damage-associated molecular pattern and neutrophil extracellular trap release, endothelial glycocalyx degradation, complement-platelet interactions, coagulation cascade activation, and impaired fibrinolysis. Lung-derived inflammatory signals cause endothelial activation and procoagulant reprogramming in distal organs following systemic dissemination, resulting in organ-specific phenotypes such as acute kidney injury, secondary myocardial injury, ARDS in the lung, neurovascular unit dysfunction, and barrier-disruption-associated inflammatory amplification along the liver-gut axis. This framework may provide a rationale for exploring stage-adapted and phenotype-guided approaches to severe viral pneumonia, including early antiviral therapy, immunomodulation during disease progression, endothelial-coagulation axis targeting, and host-directed strategies. Further longitudinal cohorts, multi-omics analyses, mechanism-based stratification studies, and mechanism-embedded clinical trials will be needed to determine whether immune-endothelial-coagulation coupling can be translated from a mechanistic model into a clinically actionable framework for precision intervention.

PMID:42698821 | PMC:PMC13542883 | DOI:10.3389/fimmu.2026.1878054