Microecology Research: A New Target for the Prevention of Asthma
Asthma, a chronic inflammatory disease of the airways characterized by hyperresponsiveness and remodeling, affects approximately 14% of children worldwide. Its rising incidence has been linked to complex interactions between genetic predisposition and environmental factors. Recent advances in sequencing technologies have unveiled the critical role of microbial communities—both environmental and human-associated—in shaping immune responses and influencing asthma development. This review synthesizes current evidence on how microecology modulates asthma pathogenesis and explores novel preventive strategies targeting microbial ecosystems.
Environmental Microbiome and Early-Life Asthma Development
The “hygiene hypothesis” posits that reduced exposure to microbial diversity in early life contributes to the increased prevalence of allergic diseases. Epidemiological studies highlight the protective effects of rural environments rich in microbial exposure. For instance, the PARSIFAL study demonstrated that prenatal exposure to farm animals elevated Toll-like receptor (TLR2, TLR4) and CD14 expression in fetal cord blood, correlating with reduced allergic sensitization. Maternal exposure to endotoxin-rich environments during pregnancy enhances neonatal immune tolerance by upregulating regulatory T cells (Tregs), which suppress pro-inflammatory T helper 2 (Th2) responses. Conversely, urbanized lifestyles and excessive cleanliness disrupt this balance, skewing immunity toward Th2-dominated pathways associated with asthma.
Air pollution, particularly fine particulate matter (PM2.5), exacerbates asthma risk. A meta-analysis revealed that each 10 μg/m³ increase in PM2.5 concentration raises childhood asthma hospitalizations by 3.45%. PM2.5 exposure during pregnancy and infancy disrupts fetal lung development, induces oxidative stress, and amplifies airway inflammation. Murine models exposed to PM2.5 showed elevated inflammatory cells (e.g., neutrophils, eosinophils) in bronchoalveolar lavage fluid (BALF) and skewed Th1/Th2 ratios toward Th2, driving interleukin (IL)-4 and IL-13 production. Similarly, paternal smoking alters DNA methylation in genes like IL10 and GSTM1, increasing offspring asthma risk by 43.48% when multiple genes are methylated.
Human Microbiome: Respiratory and Gut Ecosystems
The respiratory and intestinal microbiomes are integral to immune homeostasis. Once considered sterile, the lungs harbor dynamic microbial communities dominated by Proteobacteria, Firmicutes, and Bacteroidetes. Dysbiosis in these communities correlates with asthma severity. Asthmatic patients exhibit higher airway bacterial diversity, particularly enriched Proteobacteria, which exacerbate hyperresponsiveness. Reduced microbial diversity in infancy, detected via 16S rRNA sequencing, predicts later asthma. For example, decreased Faecalibacterium, Lachnospira, Rothia, and Veillonella in infant feces within the first 100 days post-birth is linked to heightened asthma risk.
The gut microbiome, shaped by diet, mode of delivery, and antibiotic use, profoundly influences systemic immunity. Early-life gut dysbiosis reduces Tregs and impairs immune tolerance. In murine models, specific pathogen-free (SPF) environments diminish Th1-associated interferon-gamma (IFN-γ) and elevate Th2 cytokines, promoting allergic inflammation. Maternal microbiota during pregnancy also programs fetal immunity; maternal high-fiber diets increase short-chain fatty acids (SCFAs) like acetate, which suppress allergic airway disease (AAD) in offspring by enhancing Treg function. Conversely, obesity alters gut microbiota composition, activating type 2 innate lymphoid cells (ILC2s) in the lungs via IL-1β signaling, exacerbating neutrophilic inflammation and corticosteroid resistance.
Gut-Lung Axis: Cross-Talk Between Microbial Communities
The gut and respiratory microbiomes interact bidirectionally through the gut-lung axis. Microbial metabolites, immune cells, and bacterial components (e.g., lipopolysaccharides) circulate systemically, modulating lung immunity. For instance, gut-derived SCFAs enhance pulmonary Treg activity, while dysbiosis promotes Th17-mediated inflammation. Overlap in microbial genera, such as Veillonella and Streptococcus, between the gut and airways underscores their interconnected roles. Reflux and aspiration further facilitate microbial exchange, influencing disease outcomes.
Timing and Strategies for Microbiome Modulation
The first 100 days postpartum represent a critical window for microbiome-driven asthma prevention. Early microbial colonization shapes immune maturation, with disruptions during this period increasing lifelong allergy risk. Interventions during pregnancy and infancy, such as probiotic supplementation, dietary modifications, and controlled microbial exposure, show promise.
Environmental Adjustments:
- Farm Exposure: Prenatal exposure to farm environments upregulates TLR signaling and Tregs, reducing allergic sensitization.
- Air Quality Control: Reducing PM2.5 and tobacco smoke exposure mitigates oxidative stress and inflammation.
Dietary and Microbial Interventions:
- Breastfeeding: Promotes beneficial gut microbiota (e.g., Bifidobacteria) and immune tolerance. Formula feeding correlates with dysbiosis and elevated asthma risk.
- Probiotics/Prebiotics: Lactobacillus and Bifidobacterium strains modulate Th1/Th2 balance. Maternal probiotic intake during pregnancy reduces offspring allergy risk, particularly in families with TLR genetic variants.
- High-Fiber Diets: Increase SCFA production, enhancing Treg function and suppressing eosinophilic inflammation.
Advanced Therapies:
- Fecal Microbiota Transplantation (FMT): Restores gut microbial diversity more effectively than transient probiotics, offering long-term benefits for refractory asthma.
Conclusion
Microecological research has redefined asthma as a disorder of immune-microbe interactions, influenced by environmental and host microbiomes. Key mechanisms include TLR-mediated immune regulation, Th1/Th2/Treg imbalances, and gut-lung axis cross-talk. Preventive strategies targeting microbial ecosystems during critical developmental windows—particularly prenatal and early postnatal periods—hold transformative potential. Future research must address optimal timing, duration, and methods for microbiome modulation to translate these insights into clinical practice.
doi.org/10.1097/CM9.0000000000001127
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