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

Abstract

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.