A Human Microbiome Enhanced Campylobacter Jejuni Induced Autoantibodies and Th-2 Skewing of Adaptive Immunity after Fecal Transplant

Guillain-Barré Syndrome (GBS) is a common cause of acute generalized paralysis. Infection with the enteric pathogen C. jejuni often precedes GBS when bacterial lipo-oligosaccharide resembling host nerve gangliosides activates the immune system to produce autoantibodies. We showed that C. jejuni 11168 from an enteritis patient produced T helper-1/17 responses in C57BL/6 IL-10-/- mice, while a C. jejuni GBS patient strain (260.94) blunted Th-1/17, but enhanced Th-2 responses. Only Th-2 antibodies cross-reacted with nerve gangliosides. We hypothesized that human gut microbiota (Humicrobiota) enhances immunity to C. jejuni infection with elevated C. jejuni-specific and autoantibodies. C57BL/6 germ-free mice were given a human fecal transplant, bred after gut microbiota stabilized, and their offspring used in a 30 day infection trial. Congenic Humicrobiota and mouse microbiota (Momicrobiota) mice were inoculated with C. jejuni enteritis strain 11168, GBS strain 260.94 or sham inoculated. Plasma was collected from all mice and levels of Th-1 and Th-2 antibody isotypes to nerve gangliosides and to C. jejuni strains were measured. IL-4 and IFN-g responses were measured in gut lamina propria cells by RT-PCR. Autoimmune responses were significantly elevated by the presence of Humicrobiota. Humicrobiota mice had significantly higher levels of IgG1 antibodies to C. jejuni 11168 and to GM1 and GD1a nerve gangliosides than infected Momicrobiota mice. Infected Humicrobiota mice had a 12-fold increase in IL-4 levels and decreased IFN-g levels. Humicrobiota enhanced C. jejuni induced autoantibodies to nerve gangliosides and Th-2 skewing of the adaptive immune response