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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST000338 |
| Study Title | Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease |
| Study Summary | Taxonomic 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 Name | Mathew |
| First Name | Anna |
| Address | 6112 Brehm 1000 Wall Street |
| amat@umich.edu | |
| Phone | 7342328228 |
| Submit Date | 2016-01-21 |
| Raw Data File Type(s) | d |
| Analysis Type Detail | GC-MS |
| Release Date | 2016-06-18 |
| Release Version | 1 |
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Treatment:
| Treatment ID: | TR000372 |
| Treatment Summary: | BMTs were performed as previously described {Reddy:2005dc}{Reddy:2008kl}. Briefly, syngeneic (BALB/c ? BALC/b or C57BL/6 ? C57BL/6) and allogeneic (C57BL/6 ? BALB/c or C3H.sw ? C57BL/6) recipients received lethal irradiation. On day -1, BALB/c recipients received a total of 800 cGy of irradiation (split dose separated by 3 hours) and B6 animals received a single dose of 1000 cGy. Donor splenic CD90.2+ T cells were magnetically separated using an autoMACs (Miltenyi Biotec; Bergisch Gladbach, Germany) and 0.5 x 106 – 1 x 106 T cells were transferred to BALB/c recipients and 2 x 106 T cells were transferred to C57BL/6 recipients. 5 x 106 donor whole bone marrow was transferred to all recipients. |
