Identification of extracellular vesicle microRNA signatures specifically linked to inflammatory and metabolic mechanisms in obesity‐associated low type‐2 asthma

Abstract

Rationale and ObjectivePlasma extracellular vesicles (EVs) represent a vital source of molecular information about health and disease states. Due to their heterogenous cellular sources, EVs and their cargo may predict specific pathomechanisms behind disease phenotypes. Here we aimed to utilize EV microRNA (miRNA) signatures to gain new insights into underlying molecular mechanisms of obesity‐associated low type‐2 asthma.MethodsObese low type‐2 asthma (OA) and non‐obese low type‐2 asthma (NOA) patients were selected from an asthma cohort conjointly with healthy controls. Plasma EVs were isolated and characterised by nanoparticle tracking analysis. EV‐associated small RNAs were extracted, sequenced and bioinformatically analysed.ResultsBased on EV miRNA expression profiles, a clear distinction between the three study groups could be established using a principal component analysis. Integrative pathway analysis of potential target genes of the differentially expressed miRNAs revealed inflammatory cytokines (e.g., interleukin‐6, transforming growth factor‐beta, interferons) and metabolic factors (e.g., insulin, leptin) signalling pathways to be specifically associated with OA. The miR‐17–92 and miR‐106a–363 clusters were significantly enriched only in OA. These miRNA clusters exhibited discrete bivariate correlations with several key laboratory (e.g., C‐reactive protein) and lung function parameters. Plasma EV miRNA signatures mirrored blood‐derived CD4+ T‐cell transcriptome data, but achieved an even higher sensitivity in identifying specifically affected biological pathways.ConclusionThe identified plasma EV miRNA signatures and particularly the miR‐17–92 and ‐106a–363 clusters were capable to disentangle specific mechanisms of the obesity‐associated low type‐2 asthma phenotype, which may serve as basis for stratified treatment development.

Extracellular vesicle microRNA signatures as novel biomarkers in obese asthmatics

“…The authors evaluated EV miRNAs in relation to the inflammatory and metabolic mechanisms of obese asthmatics (OA) with low type-2 asthma and compared these results to non-obese asthmatics (NOA) and healthy controls (HC) (Figure 1). 1 While results from small RNA sequencing analyses are compelling, we noted that the authors did not validate any of their findings using other approaches such as qRT-PCR and the article provides no detail on whether the total EV concentration and EV protein content were different among the three groups analyzed. Additionally, it is unclear if the EV miRNAs found in this study recapitulate what has been previously reported using similar techniques.…”

“…To the Editor, We have read, with great interest, the article recently published in Allergy, "Identification of extracellular vesicle microRNA (miRNA) signatures specifically linked to inflammatory and metabolic mechanisms in obesity-associated low-type-2 asthma". 1 We commend the authors on this exciting work on extracellular vesicles (EVs) as novel biomarkers in obese asthmatics. The authors evaluated EV miRNAs in relation to the inflammatory and metabolic mechanisms of obese asthmatics (OA) with low type-2 asthma and compared these results to non-obese asthmatics (NOA) and healthy controls (HC) (Figure 1).…”

Cow’s Milk Allergy May Induce Lipid Metabolism Disorder in BALB/c Mice via Exosomes

“…Emerging epidemiological evidence suggests a positive association between lipid metabolism disorder and the risk of allergic diseases. , High-fat diets (HFD) alter gut microbiota composition because saturated fats and cholesterol induce intestinal epithelial cells to release inflammatory mediators, thereby increasing intestinal permeability. − Inflammation of the intestinal tract is a sign of food allergy . The development of obesity is a detrimental consequence resulting from prolonged consumption of a high-fat diet (HFD), which can be attributed to the compromised integrity of the intestinal barrier. − The pro-inflammatory status observed in obese persons and disruption of the gastrointestinal barrier caused by HFD could explain the association between obesity and food allergies.…”

The importance of translational science within the respiratory field

“…Among various risk factors, obesity emerged as the main contributor, followed by depression, allergies and smoking, emphasising the necessity to address these issues to reduce hospital admissions. The fifth speaker, Holger Garn (Germany), scrutinised plasma EVs from obese and non-obese low type-2 asthma patients unveiling miRNA signatures that correlated with inflammatory cytokine and metabolic signalling pathways specific to obesity-associated low type-2 asthma patients [ 32 ]. The identified plasma EV miRNA signatures, particularly miR-17∼92 and miR-106a∼363, held potential as predictive biomarkers of obesity-associated low type-2 asthma, inversely correlating with clinical manifestations.…”