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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Project:
Project ID: | PR000270 |
Project DOI: | doi: 10.21228/M8W894 |
Project Title: | Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease |
Project 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 Center |
Email: | amat@umich.edu |
Phone: | 7342328228 |
Subject:
Subject ID: | SU000358 |
Subject Type: | Animal |
Subject Species: | Mus musculus |
Taxonomy ID: | 10090 |
Species Group: | Mammals |
Factors:
Subject type: Animal; Subject species: Mus musculus (Factor headings shown in green)
mb_sample_id | local_sample_id | Site |
---|---|---|
SA015071 | Syngeneic 4Intestine | Intestine |
SA015072 | Syngeneic 5Intestine | Intestine |
SA015073 | Allogeneic 1Intestine | Intestine |
SA015074 | Allogeneic 4Intestine | Intestine |
SA015075 | Allogeneic 3Intestine | Intestine |
SA015076 | Syngeneic 3Intestine | Intestine |
SA015077 | Syngeneic 1Intestine | Intestine |
SA015078 | Naïve 2Intestine | Intestine |
SA015079 | Naïve 1Intestine | Intestine |
SA015080 | Naïve 3Intestine | Intestine |
SA015081 | Naïve 4Intestine | Intestine |
SA015082 | Naïve 5Intestine | Intestine |
SA015083 | Syngeneic 2Intestine | Intestine |
SA015084 | Allogeneic 2Intestine | Intestine |
SA015085 | Naïve 5Liver | Liver |
SA015086 | Allogeneic 4Liver | Liver |
SA015087 | Naïve 4Liver | Liver |
SA015088 | Naïve 3Liver | Liver |
SA015089 | Naïve 1Liver | Liver |
SA015090 | Naïve 2Liver | Liver |
SA015091 | Syngeneic 2Liver | Liver |
SA015092 | Syngeneic 1Liver | Liver |
SA015093 | Syngeneic 3Liver | Liver |
SA015094 | Allogeneic 3Liver | Liver |
SA015095 | Allogeneic 2Liver | Liver |
SA015096 | Allogeneic 1Liver | Liver |
SA015097 | Syngeneic 4Liver | Liver |
SA015098 | Syngeneic 5Liver | Liver |
SA015099 | Syngeneic 5Serum | Serum |
SA015100 | Allogeneic 1Serum | Serum |
SA015101 | Syngeneic 4Serum | Serum |
SA015102 | Allogeneic 4Serum | Serum |
SA015103 | Allogeneic 3Serum | Serum |
SA015104 | Allogeneic 2Serum | Serum |
SA015105 | Syngeneic 3Serum | Serum |
SA015106 | Naïve 2Serum | Serum |
SA015107 | Syngeneic 2Serum | Serum |
SA015108 | Naïve 3Serum | Serum |
SA015109 | Naïve 1Serum | Serum |
SA015110 | Syngeneic 1Serum | Serum |
SA015111 | Naïve 4Serum | Serum |
SA015112 | Syngeneic 1Spleen | Spleen |
SA015113 | Naïve 5Spleen | Spleen |
SA015114 | Naïve 2Spleen | Spleen |
SA015115 | Syngeneic 2Spleen | Spleen |
SA015116 | Naïve 1Spleen | Spleen |
SA015117 | Naïve 3Spleen | Spleen |
SA015118 | Naïve 4Spleen | Spleen |
SA015119 | Allogeneic 3Spleen | Spleen |
SA015120 | Syngeneic 3Spleen | Spleen |
SA015121 | Allogeneic 2Spleen | Spleen |
SA015122 | Allogeneic 4Spleen | Spleen |
SA015123 | Syngeneic 4Spleen | Spleen |
SA015124 | Syngeneic 5Spleen | Spleen |
SA015125 | Allogeneic 1Spleen | Spleen |
SA015126 | Syngeneic 5Stool | Stool |
SA015127 | Allogeneic 2Stool | Stool |
SA015128 | Allogeneic 1Stool | Stool |
SA015129 | Allogeneic 3Stool | Stool |
SA015130 | Syngeneic 4Stool | Stool |
SA015131 | Allogeneic 4Stool | Stool |
SA015132 | Naïve 4Stool | Stool |
SA015133 | Naïve 2Stool | Stool |
SA015134 | Naïve 1Stool | Stool |
SA015135 | Naïve 3Stool | Stool |
SA015136 | Syngeneic 1Stool | Stool |
SA015137 | Syngeneic 2Stool | Stool |
SA015138 | Syngeneic 3Stool | Stool |
Showing results 1 to 68 of 68 |
Collection:
Collection ID: | CO000352 |
Collection Summary: | Female C57BL/6 (I-Ab; CD45.2+), BALB/c (H2d), and C3H.sw (H2b) mice were purchased from National Cancer Institute. The age of mice used for experiments ranged between 7 and 12 weeks. |
Sample Type: | Blood |
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. |
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 50µL 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. |
Combined analysis:
Analysis ID | AN000549 |
---|---|
Analysis type | MS |
Chromatography type | GC |
Chromatography system | Agilent 6890N |
Column | Phenomenex ZB-WAX |
MS Type | EI |
MS instrument type | Single quadrupole |
MS instrument name | Agilent 5973 |
Ion Mode | POSITIVE |
Units | mmol/mg |
Chromatography:
Chromatography ID: | CH000386 |
Instrument Name: | Agilent 6890N |
Column Name: | Phenomenex ZB-WAX |
Chromatography Type: | GC |
MS:
MS ID: | MS000485 |
Analysis ID: | AN000549 |
Instrument Name: | Agilent 5973 |
Instrument Type: | Single quadrupole |
MS Type: | EI |
Ion Mode: | POSITIVE |