Composition and gene functions of intestinal IgA-coated microbiota in the mouse model of chronic obstructive pulmonary disease

Abstract:

[Background] Immunoglobulin A (IgA) secreted by small airways plays a key role in the pathophysiology of chronic obstructive pulmonary disease (COPD). However, the role of IgA derived from intestinal mucosa in the pathogenesis of COPD and the IgA-coated microbiota remain unclear. [Objective] To investigate the composition, abundance, and differential gene functions of intestinal-derived IgA-coated gut microbiota in the mouse model of COPD. [Methods] A mouse model of COPD was established by intranasal instillation of lipopolysaccharide combined with cigarette smoking. Twelve fecal samples from COPD mice and 12 fecal samples from wild-type mice were collected. IgA magnetic beads were used to separate IgA-coated gut microbiota, followed by 16S rRNA gene high-throughput sequencing. [Results] We examined the modeling of COPD in mice by comparing the staining of lung tissue sections, mean linear intercept (mLI), and inflammatory cytokine concentrations in the alveolar lavage fluid between the two groups. Both OTU and PCA showed that the intestinal IgA-coated microbiota in fecal samples were different and comparable between the two groups. The alpha diversity analysis showed no statistically significant difference in the species diversity between the two groups (P>0.05). The structure of intestinal-derived IgA-coated microbiota had differences between the two groups (P<0.05). In the COPD group, the bacterial orders that were significantly enriched were Bdellovibrionales, Clostridiales, and Bifidobacteriales; the mainly enriched bacterial families were Prevotellaceae, Clostridiaceae, Paenibacillaceae, Bdellovibrionaceae, and Bifidobacteriaceae; and the mainly enriched bacterial genera were Alloprevotella, Brevibacillus, Clostridium-sensu-stricto, Turicibacter, Faecalibacterium, Vampirovibrio, and Bifidobacterium. The results of KEGG pathway enrichment analysis of differentially expressed genes showed that the cell growth and death, nucleotide metabolism, and digestive system-related pathways in the COPD group were significantly up-regulated, while the membrane transport pathway was significantly down-regulated. [Conclusion] The CODP mice present altered intestinal-derived IgA-coated gut microbiota and gene dysfunction.