Effect of Host Genetic Background on Development of Autoimmunity in Transplanted and Vertically Transmitted Human Microbiota Mouse Models

Transplanted human microbiota (Humicrobiota) dominated by Bacteroidetes and Firmicutes enhanced Type 2 autoantibody responses following Campylobacter jejuni 260.94 infection in C57BL/6 mice. We hypothesized that similar Type 2 responses occur in NOD mice given this Humicrobiota. Germ-free C57BL/6 and NOD WT mice were transplanted with young adult human fecal slurry (HFS) and bred 6+ generations. These mice and age-matched congenic specific-pathogen-free C57BL/6 and NOD WT mice with conventional microbiota (Convmicrobiota) were housed identically in concurrent infection trials. Ten mice carrying each microbiota were inoculated with either C. jejuni 11168 or 260.94 or with vehicle control. DNA from feces was subjected to Illumina MiSeq 16S sequencing. Anti-C. jejuni IgG isotype and autoantibody responses were determined by ELISA. Community compositions of the Humicrobiota and Convmicrobiota were completely distinct in both mouse strains; C. jejuni infection did not alter community structure of either microbiota in either mouse strain. The fraction of 16S reads attributable to both C. jejuni strains was elevated in both C7BL/6 and NOD Humicrobiota mice compared to the respective Convmicrobiota mice. Both C57BL/6 and NOD Humicrobiotas exhibited large increases in the genus Bacteroides compared to their respective Convmicrobiotas; Bacteroides spp. can provide energy sources preferred by C. jejuni. Type 2 C. jejuni specific antibody and autoantibody responses were significantly elevated in infected C57BL/6 but not NOD Humicrobiota mice compared to infected Convmicrobiota mice. Results demonstrate that similar Humicrobiotas were established in mice of different genetic backgrounds but their Type 2 C. jejuni-specific and autoantibody responses varied.