Summary of Study ST000338

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000270. The data can be accessed directly via it's Project DOI: 10.21228/M8W894 This work is supported by NIH grant, U2C- DK119886.

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Study IDST000338
Study TitleGut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease
Study SummaryTaxonomic alterations in the intestinal microbiota are being progressively associated with many diseases, including graft-versus host disease (GVHD). However, the impact of these alterations on microbial metabolites and by-products and their subsequent impact on disease processes, such as GVHD, are not known. Here we utilized a targetedn unbiased and blinded approach in a blinded fashion to identify novel alterations in the levels of microbial metabolites, specifically levels including the short chain fatty acid (SCFA) and endogenous histone deacetylase inhibitor (HDACi), butyrate, after allo-BMT. Surprisingly, alterations were observed only in intestinal epithelial cells (IECs) but not in the luminal contents. The reduced butyrate in IECs (CD326+) after allo-BMT resulted in decreased histone acetylation, which was restored upon local administration of exogenous butyrate. This resulted in improved IEC junctional integrity, increased anti-apoptotic proteins, decreased GVHD, and improved survival. Furthermore, alteration of endogenous microflora with 17 rationally selected strains of high butyrate producing Clostridia, also decreased GVHD and increased survival following allo-BMT in experiments performed at two different institutions. These data demonstrate an heretofore unrecognized role of microbial metabolites and suggests that local and specific alteration of microbial metabolites has direct salutary effects on GVHD target tissues and mitigates its severity.
Institute
University of Michigan
Last NameMathew
First NameAnna
Address6112 Brehm 1000 Wall Street
Emailamat@umich.edu
Phone7342328228
Submit Date2016-01-21
Raw Data File Type(s)d
Analysis Type DetailGC-MS
Release Date2016-06-18
Release Version1
Anna Mathew Anna Mathew
https://dx.doi.org/10.21228/M8W894
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Sample Preparation:

Sampleprep ID:SP000365
Sampleprep Summary:To determine targeted fatty acid quantitation, samples (plasma, spleen, liver, intestine, and intestinal fecal content) from mice 7d and 21d post-transplant were harvested, homogenized, and snap-frozen in liquid N2. Homogenized tissues were normalized to their protein content, while 50┬ÁL of plasma was used per sample and Equal volumes of plasma and homogenized tissue were utilized, while50 mg fecal content was weighed at necropsy before extraction. Samples were dispersed in acidified water spiked with stable isotope-labeled SCFA standards and extracted with diethyl ether.
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