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Clostridium sporogenes-derived metabolites protect against colonic inflammation

ABSTRACT: Clostridium sporogenes-derived metabolites protect against colonic inflammation

PROVIDER: PRJNA1100564 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28699911.fastq.gz	Fastqsanger.gz
	SRR28699912.fastq.gz	Fastqsanger.gz
	SRR28699913.fastq.gz	Fastqsanger.gz
	SRR28699914.fastq.gz	Fastqsanger.gz
	SRR28699915.fastq.gz	Fastqsanger.gz

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Clostridium sporogenes-derived metabolites protect against colonic inflammation

Project description:Purpose: Gut microbiota-derived metabolites play a pivotal role in the maintenance of local gut homeostasis and can even induce systemic effects via accumulation in the bloodstream. Here, we demonstrate that mono-colonization of germ-free (GF) mice with Clostridium sporogenes protects mice from inflamation and death induced by DSS colitis. Method: 8-12-week-old male mice (GF, SPF and GF colonized with C. sporogenes (CS)) were treated with 2.5% DSS in drinking water for 5 days and colon tissue was isolated on day 7. RNA was isolated from the colon tissue and RNA sequenzing was performed. Results: Mono-colonization of GF mice with Clostridium sporogenes protected the mice from DSS colitis induced death, while producing high amounts of indole-3-propionic acid (IPA), branched chain (BCFA) and short-chain (SCFA) fatty acids. In comparison to CS mice, SPF mice showed much higher levels of inflammatory related genes and a worse histological score. Conclusion: Histological stainings and the RNAseq both showed high levels of protection of C. sporogenes colonized mice in colitis, compared to SPF and GF animals. The data provide evidence for a therapeutic potential of C. sporogenes for IBD patients.

2024-10-15 | GSE264024 | GEO

<i>Clostridium sporogenes</i>-derived metabolites protect mice against colonic inflammation.

Project description:Gut microbiota-derived metabolites play a pivotal role in the maintenance of intestinal immune homeostasis. Here, we demonstrate that the human commensal Clostridium sporogenes possesses a specific metabolic fingerprint, consisting predominantly of the tryptophan catabolite indole-3-propionic acid (IPA), the branched-chain acids (BCFAs) isobutyrate and isovalerate and the short-chain fatty acids (SCFAs) acetate and propionate. Mono-colonization of germ-free mice with C. sporogenes (CS mice) affected colonic mucosal immune cell phenotypes, including up-regulation of Il22 gene expression, and increased abundance of transcriptionally active colonic tuft cells and Foxp3+ regulatory T cells (Tregs). In DSS-induced colitis, conventional mice suffered severe inflammation accompanied by loss of colonic crypts. These symptoms were absent in CS mice. In conventional, but not CS mice, bulk RNAseq analysis of the colon revealed an increase in inflammatory and Th17-related gene signatures. C. sporogenes-derived IPA reduced IL-17A protein expression by suppressing mTOR activity and by altering ribosome-related pathways in Th17 cells. Additionally, BCFAs and SCFAs generated by C. sporogenes enhanced the activity of Tregs and increased the production of IL-22, which led to protection from colitis. Collectively, we identified C. sporogenes as a therapeutically relevant probiotic bacterium that might be employed in patients with inflammatory bowel disease (IBD).

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Comparative genomic hybridization of 61 strains of proteolytic Clostridium botulinum or Clostridium sporogenes

Project description:Genomic DNA of 61 strains of proteolytic Clostridium botulinum or Clostridium sporogenes was subjected to analysis by DNA microarray.

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