1302 The therapeutic effect of glycolysis inhibition in lupus-prone mice is transferable through the fecal microbiome

Gut microbial dysbiosis has been reported in patients with lupus. Results obtained mouse models suggest that contributes to lupus pathogenesis through the pathobionts induce inflammation by translocating out of gut and/or producing proinflammatory metabolites. We and others have shown fecal microbiota transfers (FMT) from lupus-prone mice induced autoantibodies immune activation non-autoimmune mice. On other hand, we production associated expansion follicular T (Tfh) cells germinal center (GC) B can be eliminated treating 2-deoxy-D-glucose (2DG), a glycolysis inhibitor. Here, investigated effect 2DG on microbiome two different etiologies, (NZB × NZW)F1 (NZW x BXSB)F1 Anti-dsDNA IgG-positive were treated 2DG. The composition their was determined 16S rDNA sequencing metabolome LC-MS analysis, compared age-matched controls. Fecal samples these used for FMT 3 times per week pre-autoimmune same strain pre-treated antibiotics 2 weeks. lasted 26 weeks 9 Age-matched controls gavaged PBS. Autoantibodies measured ELISA indirect immunofluorescence. Immunophenotypes assessed flow cytometry spleen mesenteric lymph nodes. Renal pathology evaluated light microscopy PAS-stained sections immunofluorescence frozen antibodies complement C3, IgG2a, F4/80 CD3. showed treatment started reduced changes bacterial populations occurred as disease developed control both models. also altered distribution metabolites Next, serial 2DG-treated or into antibiotics. In models, protective, reduction anti-dsDNA IgG production, cell activation, renal Overall, our results demonstrated first time therapeutic glucose inhibition is transferable microbiota. These enhanced metabolism promotes pathogenic bacteria either directly indirectly system normalized inhibition. Lay summary High sustains Inhibition drug called reverses Here lupus- prone Further, protected younger develop significantly effects lupus, beneficial reducing includes restoration healthy microbiome.