Respiratory Microbiota Profiles Associated With the Progression From Airway Inflammation to Remodeling in Mice With OVA-Induced Asthma

Abstract

BackgroundThe dysbiosis of respiratory microbiota plays an important role in asthma development. However, there is limited information on the changes in the respiratory microbiota and how these affect the host during the progression from acute allergic inflammation to airway remodeling in asthma.ObjectiveAn ovalbumin (OVA)-induced mouse model of chronic asthma was established to explore the dynamic changes in the respiratory microbiota in the different stages of asthma and their association with chronic asthma progression.MethodsHematoxylin and eosin (H&E), periodic acid-schiff (PAS), and Masson staining were performed to observe the pathological changes in the lung tissues of asthmatic mice. The respiratory microbiota was analyzed using 16S rRNA gene sequencing followed by taxonomical analysis. The cytokine levels in bronchoalveolar lavage fluid (BALF) specimens were measured. The matrix metallopeptidase 9 (MMP-9) and vascular endothelial growth factor (VEGF-A) expression levels in lung tissues were measured to detect airway remodeling in OVA-challenged mice.ResultsAcute allergic inflammation was the major manifestation at weeks 1 and 2 after OVA atomization stimulation, whereas at week 6 after the stimulation, airway remodeling was the most prominent observation. In the acute inflammatory stage, Pseudomonas was more abundant, whereas Staphylococcus and Cupriavidus were more abundant at the airway remodeling stage. The microbial compositions of the upper and lower respiratory tracts were similar. However, the dominant respiratory microbiota in the acute inflammatory and airway remodeling phases were different. Metagenomic functional prediction showed that the pathways significantly upregulated in the acute inflammatory phase and airway remodeling phase were different. The cytokine levels in BALF and the expression patterns of proteins associated with airway remodeling in the lung tissue were consistent with the metagenomic function results.ConclusionThe dynamic changes in respiratory microbiota are closely associated with the progression of chronic asthma. Metagenomic functional prediction indicated the changes associated with acute allergic inflammation and airway remodeling.

Shared and Specific Lung Microbiota with Metabolic Profiles in Bronchoalveolar Lavage Fluid Between Infectious and Inflammatory Respiratory Diseases

“…The present study had some limitations. First, in all identified ASVs, the proportion of "unassigned" in the BALF samples reached 35% and varied from 10% to 40% in the previous studies, 37,48,49 which may be caused by the imperfect recall (not all sequences or taxa are detected) or imperfect precision (additional false sequences or taxa are detected) of the 16S V3-V4 rRNA sequencing. 50 Meanwhile, the different phenomena of species within genera highlight the interspecies variability that complicates microbiome data interpretation, so it is important to identify organisms at the species level.…”

“…We found that some gut-associated bacteria were specifically more abundant in CAP patients, and previous studies have indicated that increased lung and gut permeability may induce bacterial migration in various respiratory diseases, such as acute respiratory disease syndrome (ARDS). 33,36 Besides, Pseudomonas, which is a frequent pathogenic colonizer in COPD and asthma patients 37 and predispose the host to more severe respiratory viral pneumonia, 38 was increased in the CAP group and correlated with CRP level. Exoproteins from Pseudomonas were reported to disrupt the mucosal barrier and induce IL-6 production potentially contributing to mucosal inflammation.…”

“…39 Thus, in CAP patients even without ARDS, the overgrowth of certain pathogens under acute infection may lead to the breakdown of the lung barrier and the induction of gutlung bacterial translocation, which further correlates with more severe inflammation. 33,37,38,40 In the CTD-ILD group, many putative commensal microbes, such as Veillonella and Streptococcus, were enriched compared with HC. Streptococcus intermedius enrichment was associated with increased ESR.…”

Anti-inflammatory activities of Qingfei oral liquid and its influence on respiratory microbiota in mice with ovalbumin-induced asthma

“…In our previous study (Zheng et al, 2021), dynamic observation of OVA-induced asthmatic mouse models showed that the 2week phase of nebulization was the transition from eosinophilic inflammation to neutrophil inflammation and the initiation of small airway remodeling, so we selected the asthmatic mouse model during this critical transition period for our study. Many previous studies (Lönnkvist et al, 2001;Wenzel et al, 2016) have shown that Budesonide has a unique advantage for eosinophil asthma.…”

Biologics and Airway Remodeling in Severe Asthma

“…A recent study in a mouse model of asthma demonstrated dynamic changes in the respiratory microbiota at different stages of the disease. In particular, Staphylococcus and Cupriavidus were more abundant during airway remodeling 110 . Additional studies are urgently needed to investigate whether the dysbiosis of airway microbiota could also play a role in the progression from allergic inflammation to airway remodeling in humans.…”