GSE138330 Ampicillin treatment casues dysbiosis that persists until study endpoint [RNA-seq]

Contributors : Julie Tarrant ; Matthew CormierSeries Type : Expression profiling by high throughput sequencingOrganism : mouse gut metagenomeThe development of neutralizing FVIII antibodies is the most serious complication of hemophilia A treatment. The currently known patient- and treatment-related risk factors for inhibitor development do not accurately predict this adverse event in all patients. The composition of the gut microbiota has been shown to influence immune mediated diseases at distant anatomical sites (e.g. lungs, brain and joints). We demonstrate that a disrupted gut microbiome can be created in a mouse model of hemophilia A using a broad-spectrum antibiotic. Under controlled conditions, this sustained dysbiosis was associated with an enhanced anti-FVIII immune response as evidenced by increased splenic B cells and the development of higher titre FVIII specific IgG antibodies following FVIII challenge. Splenic and mesenteric lymph node cytokines, T cells and dendritic cells were unaffected prior to FVIII administration. However, the immune transcriptome of both aforementioned secondary lymphoid organs was significantly modified. Short chain fatty acids (SCFA), which are microbial metabolites, were depleted in cecal contents of the dysbiotic mice. Furthermore, supplementation of the drinking water with the most immunologically active SCFA, butyrate, successfully achieved attenuation of the FVIII immune response. Collectively, our data suggest that the composit...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing mouse gut metagenome Source Type: research