Summary of Study ST002345

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 PR001505. The data can be accessed directly via it's Project DOI: 10.21228/M85717 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

Perform statistical analysis  |  Show all samples  |  Show named metabolites  |  Download named metabolite data  
Download mwTab file (text)   |  Download mwTab file(JSON)   |  Download data files (Contains raw data)
Study IDST002345
Study TitleStress-Induced Mucosal Layer Disruption Drives Gut Dysbiosis and Depressive-like Behaviors
Study SummaryDepression is a common mental health condition with a large social and economic impact. While depression etiology is multifactorial, chronic stress is a well-accepted contributor to disease onset. In addition, depression is associated with altered gut microbial signatures that can be replicated in animal models. While targeted restoration of the microbiome has been shown to reduce depressive-like behaviors in mice, the complexity and diversity of the human microbiome has complicated therapeutic intervention in patients. To circumvent these limitations, there is a critical need for identifying pathways responsible for microbiome dysbiosis. Here, for the first time, we identify the changes in host physiology that induce microbiome dysbiosis. Specifically, we show that a component of mucosal layer, the transmembrane protein mucin 13, can regulate microbiome composition. Using a model of chronic stress to induce behavioral and microbial changes in mice, we show a significant reduction in mucin 13 expression across the intestines that occurs independently of the microbiome. Furthermore, deleting Muc13 leads to gut dysbiosis, and baseline behavioral changes normally observed after stress exposure. Together, these results validate the hypothesis that mucosal layer disruption is an initiating event in stress-induced dysbiosis and offer mucin 13 as a potential new therapeutic target for microbiome dysbiosis in stress-induced depression. For the first time, our data provide an upstream and conserved target for treating microbiome dysbiosis, a result with sweeping implications for diseases presenting with microbial alterations.
Institute
University of Virginia
Last NameRivet-Noor
First NameCourtney
Address409 Lane Road, Charlottsville, Virginia, 22903, USA
Emailcrr4tz@virginia.edu
Phone434-243-1903
Submit Date2022-11-10
Num Groups2
Total Subjects23
Num Males23
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2022-11-28
Release Version1
Courtney Rivet-Noor Courtney Rivet-Noor
https://dx.doi.org/10.21228/M85717
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Sample Preparation:

Sampleprep ID:SP002440
Sampleprep Summary:Whole blood was extracted from animals at the time of euthanization from the heart chamber. Blood was collected into blood collection tubes (Fisher Scientific; #02-675-185) and spun for 10 min at 11,000g. Serum was collected and frozen in liquid nitrogen. 25uL of plasma was extracted with 500uL of acetonitrile by vortexing and centrifugation at 10min at 14,000rpm. 450uL of supernatant was transferred to new tube and dried via SpeedVac. Dried samples were reconstituted with 25uL of 50% methanol and transferred to autosampler vials. Injection volume =10uL in PRM mode for detection and quantification of 10 different analytes. Metabolite mixture was analyzed on Thermo Orbitrap IDX MS system coupled to a Vanquish UPLC system. Samples were transported via the autosampler (10uL injection volume) onto a Waters BEH C18 column. Runtime was 15min in PRM mode. Buffer A: 0.1% formic acid in water. Buffer B: 0.1% formic acid in methanol. LC Gradient: 0min: 0% B, 8min: 50% B, 9 min: 98% B, 13min: 98% B. Recalibration of system up to 15 min at 0% B for next injection.
Processing Storage Conditions:Described in summary
Extract Storage:Described in summary
  logo