2025-05-12
When miRNAs take the lead
Pneumonology
#Asthma #miRNA #Metabolome #Inflammation
#BronchialObstruction
Childhood asthma is a chronic inflammatory disease of the airways, characterized by variable airflow obstruction, airway hyperresponsiveness (AHR), and eosinophilic inflammation. This condition, whose severity and symptoms vary widely between individuals, is one of the leading causes of pediatric respiratory morbidity worldwide. Despite progress in the classification of clinical phenotypes and the availability of therapeutic options, the molecular mechanisms underlying the heterogeneity of the disease remain poorly understood.
MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression post-transcriptionally, play a central role in orchestrating immune and inflammatory responses. At the same time, metabolites—end products or intermediates of cellular metabolism—reflect the complex interactions between genes, environment, and pathophysiological states. While each of these elements has been studied individually in the context of asthma, the cross-interaction between miRNAs and the metabolome had not yet been examined in an integrated, large-scale analysis.
This is precisely the aim of this innovative study, which leverages a combined multi-omic approach by integrating miRNAome and metabolome data from two large, independent pediatric cohorts (CAMP and GACRS). It seeks to identify robust associations between miRNA-metabolite profiles and key clinical phenotypes of asthma—particularly eosinophilia, bronchial obstruction, and hyperresponsiveness—in order to better understand the molecular regulatory networks involved in disease expression.
To decipher the molecular mechanisms behind various clinical manifestations of pediatric asthma, this study performed an integrative analysis using a miRNAome-metabolome wide association study (miMWAS) in two large independent cohorts of asthmatic children. This multi-omic approach aimed to identify cross-interactions between circulating microRNA (miRNA) profiles and plasma metabolites, focusing on three key phenotypes: blood eosinophilia, bronchial hyperresponsiveness, and airway obstruction.
The analysis revealed 369 significant associations between 133 miRNAs and 60 metabolites, highlighting the existence of complex interaction networks. Among these, 13 metabolites and 4 miRNAs were identified as central hubs, suggesting a pivotal role in regulating biological functions related to asthma. The most involved molecules include taurine, 12,13-diHOME, 9-cis retinoic acid, and cortisol. Notably, nine associations remained stable over a four-year period, reinforcing their value as potential biomarkers.
Additionally, mediation analysis highlighted five key metabolites mediating the effects of 59 miRNAs on the three major clinical asthma phenotypes. Among these mediators, taurine and 12,13-diHOME emerged as particularly central. Their metabolic pathways are targeted by specific miRNAs that regulate gene expression involved in inflammatory responses, bronchial remodeling, and immune tolerance. These findings suggest a tight functional link between miRNA-mediated post-transcriptional regulation, metabolic alterations, and the clinical expression of childhood asthma.
Pediatric asthma is a chronic inflammatory disease of the airways, with biological mechanisms that remain only partially understood. One of the main current challenges lies in understanding the molecular factors that determine phenotype variability, particularly eosinophilia, bronchial obstruction, and airway hyperresponsiveness. In this context, exploring new biological pathways becomes essential to refine diagnosis, predict clinical trajectories, and develop more targeted treatments.
This study aimed to assess the cross-associations between microRNA profiles and the metabolome in children with asthma, in order to better understand their combined impact on the disease’s clinical manifestations. The results show that certain miRNAs influence key asthma phenotypes through specific metabolic pathways, acting as indirect regulators of pulmonary and immune homeostasis. The linoleic acid and vitamin A pathways, in particular, emerge as central regulatory circuits.
These findings open promising perspectives for identifying diagnostic and prognostic biomarkers, as well as developing new therapeutic targets within a precision medicine framework. However, several limitations should be considered: metabolomic coverage remains partial, the analyses are limited to two cohorts, and the results require functional validation. Further studies in independent and diverse cohorts are essential to confirm the robustness of the identified associations. Expanding integrated multi-omic approaches—combining transcriptomics, metabolomics, and environmental exposure—could deepen our understanding of asthma mechanisms. These efforts lay the groundwork for a new integrated approach to pediatric asthma at the intersection of genomics, metabolism, and immunoregulation.
Childhood asthma is a chronic inflammatory disease of the airways, characterized by variable airflow obstruction, airway hyperresponsiveness (AHR), and eosinophilic inflammation. This condition, whose severity and symptoms vary widely between individuals, is one of the leading causes of pediatric respiratory morbidity worldwide. Despite progress in the classification of clinical phenotypes and the availability of therapeutic options, the molecular mechanisms underlying the heterogeneity of the disease remain poorly understood.
MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression post-transcriptionally, play a central role in orchestrating immune and inflammatory responses. At the same time, metabolites—end products or intermediates of cellular metabolism—reflect the complex interactions between genes, environment, and pathophysiological states. While each of these elements has been studied individually in the context of asthma, the cross-interaction between miRNAs and the metabolome had not yet been examined in an integrated, large-scale analysis.
This is precisely the aim of this innovative study, which leverages a combined multi-omic approach by integrating miRNAome and metabolome data from two large, independent pediatric cohorts (CAMP and GACRS). It seeks to identify robust associations between miRNA-metabolite profiles and key clinical phenotypes of asthma—particularly eosinophilia, bronchial obstruction, and hyperresponsiveness—in order to better understand the molecular regulatory networks involved in disease expression.
Which miRNA matches which breath?
To decipher the molecular mechanisms behind various clinical manifestations of pediatric asthma, this study performed an integrative analysis using a miRNAome-metabolome wide association study (miMWAS) in two large independent cohorts of asthmatic children. This multi-omic approach aimed to identify cross-interactions between circulating microRNA (miRNA) profiles and plasma metabolites, focusing on three key phenotypes: blood eosinophilia, bronchial hyperresponsiveness, and airway obstruction.
The analysis revealed 369 significant associations between 133 miRNAs and 60 metabolites, highlighting the existence of complex interaction networks. Among these, 13 metabolites and 4 miRNAs were identified as central hubs, suggesting a pivotal role in regulating biological functions related to asthma. The most involved molecules include taurine, 12,13-diHOME, 9-cis retinoic acid, and cortisol. Notably, nine associations remained stable over a four-year period, reinforcing their value as potential biomarkers.
Additionally, mediation analysis highlighted five key metabolites mediating the effects of 59 miRNAs on the three major clinical asthma phenotypes. Among these mediators, taurine and 12,13-diHOME emerged as particularly central. Their metabolic pathways are targeted by specific miRNAs that regulate gene expression involved in inflammatory responses, bronchial remodeling, and immune tolerance. These findings suggest a tight functional link between miRNA-mediated post-transcriptional regulation, metabolic alterations, and the clinical expression of childhood asthma.
Read next: The role of psychological interventions in asthma management
Asthma rewritten in molecular code
Pediatric asthma is a chronic inflammatory disease of the airways, with biological mechanisms that remain only partially understood. One of the main current challenges lies in understanding the molecular factors that determine phenotype variability, particularly eosinophilia, bronchial obstruction, and airway hyperresponsiveness. In this context, exploring new biological pathways becomes essential to refine diagnosis, predict clinical trajectories, and develop more targeted treatments.
This study aimed to assess the cross-associations between microRNA profiles and the metabolome in children with asthma, in order to better understand their combined impact on the disease’s clinical manifestations. The results show that certain miRNAs influence key asthma phenotypes through specific metabolic pathways, acting as indirect regulators of pulmonary and immune homeostasis. The linoleic acid and vitamin A pathways, in particular, emerge as central regulatory circuits.
These findings open promising perspectives for identifying diagnostic and prognostic biomarkers, as well as developing new therapeutic targets within a precision medicine framework. However, several limitations should be considered: metabolomic coverage remains partial, the analyses are limited to two cohorts, and the results require functional validation. Further studies in independent and diverse cohorts are essential to confirm the robustness of the identified associations. Expanding integrated multi-omic approaches—combining transcriptomics, metabolomics, and environmental exposure—could deepen our understanding of asthma mechanisms. These efforts lay the groundwork for a new integrated approach to pediatric asthma at the intersection of genomics, metabolism, and immunoregulation.
Read next: MicroRNAs & Microbiota: An Inflammatory Duo?
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