Summary of project PR002557

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 PR002557. The data can be accessed directly via it's Project DOI: 10.21228/M84C32 This work is supported by NIH grant, U2C- DK119886.

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

Project ID: PR002557
Project DOI:doi: 10.21228/M84C32
Project Title:Intestine-derived sorbitol drives steatotic liver disease in the absence of gut bacteria
Project Summary:The role of the gut microbiome in mediating steatotic liver disease is poorly understood. Here, we developed a model to deplete the gut microbiome in adult zebrafish and discovered that it led to steatotic liver disease in animals on standard diets. Using metabolomics and isotope tracing, we found that dietary glucose is transformed into sorbitol within the intestine. While bacteria degrade the sorbitol in control animals, sorbitol is passed to the livers of fish in which the gut microbiome has been depleted. Within the liver, sorbitol is converted into fructose 1-phosphate, which subsequently activates glucokinase. The result is increased hepatic metabolism of glucose, leading to elevated glycogen and fat content. Inhibition of sorbitol production in microbiome-depleted animals was sufficient to prevent the development of steatotic liver, and colonizing sorbitol-degrading bacteria in the intestines of microbiome-depleted fish reversed the steatotic liver phenotype. Taken together, these findings show that sorbitol-degrading bacteria in the gut protect against steatotic liver disease.
Institute:Washington University in St. Louis
Last Name:Jackstadt
First Name:Madelyn
Address:One Brookings Drive, St. Louis, Missouri, 63130, USA
Email:mjackstadt@wustl.edu
Phone:3149356405

Summary of all studies in project PR002557

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
Release
Date
VersionSamplesDownload
(* : Contains raw data)
ST004074 Metabolite Pools in Adult Zebrafish Treated with Antimicrobials or Control Danio rerio Washington University in St. Louis MS 2025-10-28 1 288 Uploaded data (5.9G)*
ST004075 [U-13C]Glucose Labeling in Adult Zebrafish Treated with Antimicrobials or Control Danio rerio Washington University in St. Louis MS 2025-10-28 1 44 Uploaded data (401.5M)*
ST004076 [U-13C]Sorbitol Labeling in Adult Zebrafish Treated with Antimicrobials or Control Danio rerio Washington University in St. Louis MS 2025-10-28 1 22 Uploaded data (203.8M)*
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