Aggravation of airway inflammation in RSV-infected asthmatic mice following infection-induced alteration of gut microbiota.

BACKGROUND: This study aimed to confirm the relationship between asthma, respiratory syncytial virus (RSV) infection, and the gut environment by analyzing the alterations in the gut microbiota of RSV-infected asthmatic mice. METHODS: Twenty-four male BALB/c mice were randomly separated into a control group (CON), ovalbumin (OVA) group, and an OVA + RSV group, (n=8 mice/group). At the end of experiments, we evaluated the RSV-infected asthma model using Wright-Giemsa staining, histopathology and immunoglobulin E (IgE) level using enzyme-linked immunosorbent assays (ELISA). Next, airway hyper-responsiveness (AHR) was measured using Buxco's modular and invasive system. Furthermore, IL cytokine expression were measured using ELISA. Moreover, feces were collected for 16S ribosome RNA (16S rRNA) sequencing and data analysis. RESULTS: We observed that the total BAL fluid lung cells in the OVA + RSV group was significantly higher than other group. We revealed that the inflammatory infiltration, edema, and collagen hyperplasia were more severe in the OVA + RSV group. The AHR of RSV-infected mice was aggravated compared with the other groups, (P<0.05 and P<0.01). We observed a higher expression of IgE, interleukin (IL)-5, IL-13, IL-25, and IL-33 levels in mice from the OVA and OVA + RSV groups (P<0.05 and P<0.01). The associations between Prevotellaceae_UCG_001, which is positive, and IgE, IL-13, IL-33 (P<0.001), IL-5 (P<0.01), and IL-25 (P<0.05) were highly significant. Lachnospiraceae_NK4A136_group is also positive and was significantly associated with IgE and IL-33. Helicobacter and Uncultured_Bacteroidales_bacteriumare_group, which are negative, were associated with IL-25 (P<0.05). CONCLUSIONS: Our results indicated that RSV-infected mice with asthma may have changes in the gut microbiota's major components and may influence the mutual relationship between the core operational taxonomic units (OTUs) and IgE as well as inflammatory cytokines.

Qingfei oral liquid alleviates airway hyperresponsiveness and mucus hypersecretion via TRPV1 signaling in RSV-infected asthmatic mice.

Pediatric asthma is exacerbated by Respiratory Syncytial Virus (RSV) infection, and Transient Receptor Potential Vanilloid 1 (TRPV1) promotes production of inflammatory cytokines and mucus hypersecretion in the pathology of this disease. Our previous research revealed that Qingfei oral liquid (QF) inhibited airway inflammation and mucus hypersecretion in RSV-infected asthmatic mice models and that this may be associated with the TRPV1-regulation of NF-κB and Mucin 5AC (MUC5AC) expression, but the exact mechanism is unknown. In the present study, LC-MS was used for analyzing the chemicals in QF, ovalbumin (OVA)-induced asthmatic mice inhaled RSV three consecutive times to create an RSV-infected asthmatic model. We found treatment from QF alleviated airway hyperresponsiveness (AHR) and reduced congestion, edema, and infiltration of inflammatory cells into pulmonary tissues. Additionally, QF was found to decrease expression of NF-κB and its downstream inflammatory cytokines IL-1ß, IL-4, IL-5, and IL-13, as well as a decrease in MUC5AC and pro-inflammatory cytokines in PKC via a reduction in Protein Kinase C-dependent signaling. These findings suggest that QF can alleviate AHR and mucus hypersecretion caused by RSV infection in asthmatic mice, and its mechanism may be associated with the regulation of the TRPV1 signaling pathway.