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ABSTRACT: EMG produced TPA metagenomics assembly of PRJEB23524 data set (WGS data from FMT trial for the treatment of recurrent Clostridium difficile infection).

PROVIDER: PRJEB44032 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR2198657.fasta.gz	Fasta.gz
	ERR2198703.fasta.gz	Fasta.gz
	ERR2198712.fasta.gz	Fasta.gz
	ERR2198646.fasta.gz	Fasta.gz
	ERR2198615.fasta.gz	Fasta.gz

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Project description:EMG produced TPA metagenomics assembly of PRJNA285502 data set (Fecal microbiota transplantation (FMT) for ulcerative colitis).

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Microbiota-dependent IL-33 restricts the virulence of binary toxin expressing epidemic Clostridium difficile via ILC2s.

Project description:Hypervirulent epidemic strains of Clostridium difficile (C. difficile), referred to as NAPI/027, express an additional virulence factor, binary toxin (CDT), and are associated with more severe disease. Emerging evidence indicates gut immunity to C. difficile is a delicate balance between protection and pathology. To identify potential therapeutic host immune targets, we conducted a transcriptome analysis of host genes altered by NAPI/027 infection and identified interleukin-33 (IL-33) as a candidate immune target. Using a murine model, we show that both endogenous IL-33 and exogenous IL-33 treatment protect from the enhanced mortality, weight-loss and tissue pathology which is characteristic of hypervirulent C. difficile. IL-33 mediated protection was elicited through type-2 innate lymphoid cells (ILC2s) and adoptive transfer of purified ILC2s was sufficient to mitigate CDI- associated mortality and weight-loss. Furthermore, dysregulated IL-33 signaling via the soluble IL-33 decoy receptor (sST2) predicted disease severity and mortality in human patients. Lastly, colonic IL-33 expression appears to be regulated by the microbiota as antibiotic- depletion of IL-33 was rescued with mouse fecal microbiota transplant (FMT) and a human fecal spore preparation (HSP). Thus, IL-33 signaling is a novel therapeutic pathway for severe CDI which can potentially be targeted with rationally designed microbial therapies.

2019-05-09 | GSE122013 | GEO

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