Transplanted human fecal microbiota enhanced Guillain Barré syndrome autoantibody responses after Campylobacter jejuni infection in C57BL/6 mice

• DOI: 10.1186/s40168-017-0284-4
• Publication Date: 2017-08-08T14:00:16Z
• Authors: Phillip T. Brooks; Kelsey A. Brakel; Julia A. Bell; Christopher E. Be...; Trey Gilpin; Jean M. Brudvig; Linda S. Mansfield
• Keywords: Molecular mimicry

Campylobacter jejuni is the leading antecedent infection to autoimmune neuropathy Guillain-Barré syndrome (GBS), which accompanied by an anti-ganglioside antibody attack on peripheral nerves. Previously, we showed that contrasting immune responses mediate C. induced colitis and autoimmunity in interleukin-10 (IL-10)-deficient mice, dependent upon infecting strain. Strains from patients elicited T helper 1 (TH1)-dependent inflammatory while strains GBS TH2-dependent autoantibody production. Both syndromes were exacerbated antibiotic depletion of microbiota, but other factors controlling susceptibility are unknown.Using 16S rRNA gene high-throughput sequencing, examined whether structure gut microbial community alters host (1) gastrointestinal inflammation or (2) after with patients. We compared these C57BL/6 mice either stable human microbiota (Humicrobiota) transplants conventional mouse (Convmicrobiota).Inoculating germ-free wild-type (WT) a mixed fecal slurry provided murine model stably passed its over >20 generations. Mice housed specific pathogen-free (SPF) facilities, extra precautions having caretakers wear sterile garb along limited access ensured no pathogens acquired. Humicrobiota conferred many changes WT contrast previous results, only colonization disease challenge. When Convmicrobiota for enteric patient strains, infected had 10-100 fold increases both pathologic change draining lymph nodes mild colon cecal lamina propria, (3) significantly lower Th1/Th17-dependent anti-C. responses, (4) higher IL-4 at 5 not 7 weeks post (PI), (5) Th2-dependent (6) elevated autoantibodies infection. These correlated dominant Bacteroidetes Firmicutes microbiota.These data demonstrate altered host-pathogen interactions increasing Th-2 strain-dependent manner. Thus, composition another factor GBS.