Host-Microbiota Communication in Spontaneously Hypertensive Rats Generates Unique IgA-Coated Gut Microbes

Background: Hypertension is associated with gut dysbiosis, altered intestinal immunity, and gut pathology in animal models and humans. Although these findings have implicated impaired interactions between gut and gut microbiota in hypertension, little is known about the specific functional gut microbes that interact with intestinal mucosa. Methods and Results: To identify these microbes, we sorted Immunoglobin A (IgA)-coated (IgA(+)) and IgA-noncoated (IgA(-)) bacteria using a combination of magnetic-activated cell sorting and fluorescence-activated cell sorting, and subsequently performed 16 S rRNA gene sequencing (IgA-SEQ) to determine the microbial composition of IgA(+) and IgA(-) fractions in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats. We observed a significant decrease in IgA(+) bacteria in SHR compared with Wistar Kyoto and a distinct composition of IgA(+) and IgA(-) bacteria between Wistar Kyoto and SHR, showing more IgA-bound Proteobacteria, Bacteroidetes and Actinobacteria but less of Firmicutes in SHR at the phylum level. We further identified enriched IgA-coated Romboutsia, Turicibacter, Ileibacterium, and Dubosiella in SHR that were negatively correlated with the various pathways including antigen presentation, immune response, cell junction organization, epithelium development, and defense response to virus. Conclusions: We demonstrate new IgA-coated bacteria that participate in host-microbiota communication in hypertension, suggesting promising therapeutic interventions targeting these bacteria for hypertension management.

Automated summary

Hypertension is associated with gut dysbiosis and altered intestinal immunity. Using sorting techniques and gene sequencing, we found significant differences in IgA(+) and IgA(-) bacteria between hypertensive and normotensive rats. We also identified several IgA-coated bacteria that were negatively correlated with various pathways involved in immune response and epithelium development.