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

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

PROVIDER: PRJNA575802 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10218525_1.fastq.gz	Fastqsanger.gz
	SRR10218525_2.fastq.gz	Fastqsanger.gz
	SRR10218526_1.fastq.gz	Fastqsanger.gz
	SRR10218526_2.fastq.gz	Fastqsanger.gz
	SRR10218527_1.fastq.gz	Fastqsanger.gz

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

Project description:The 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 composition of the gut microbiome alters the FVIII immune response via the action of specific microbial metabolites on the immune cell transcriptome and that oral butyrate supplementation effectively reduces the FVIII immune response. Mice treated with one week of ampicillin at 3 weeks of age have a dysbiotic gut microbiome at 6 weeks of age and at the study endpoint. The immune response to FVII was compared between the two cohorts. The dysbiotic cohort had a greater immune response to FVIII

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Gut microbiota dysbiosis rewires host mRNA m6A epitranscriptomic landscape via bile acid metabolism

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Ampicillin treatment casues dysbiosis that affects transcriptome in spleen and mesenteric lymph nodes [nCounter Mouse Immunology Panel]

Project description:The 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 composition of the gut microbiome alters the FVIII immune response via the action of specific microbial metabolites on the immune cell transcriptome and that oral butyrate supplementation effectively reduces the FVIII immune response. Mice treated with one week of ampicillin at 3 weeks of age have a dysbiotic gut microbiome throughout the study and an enhanced immune response to FVIII which was administered at 6 weeks of age. Here we assess the immune transcriptome in the mice spleen and Mesenteric lymph nodes at 6 weeks of age, just prior to exposure to FVIII challenge.

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Ampicillin treatment casues dysbiosis that affects transcriptome in spleen and mesenteric lymph nodes [nCounter Mouse Immunology Panel]

Project description:Ampicillin treatment casues dysbiosis that affects transcriptome in spleen and mesenteric lymph nodes [nCounter Mouse Immunology Panel]

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