Summary of Study ST004076
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
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.
| Study ID | ST004076 |
| Study Title | [U-13C]Sorbitol Labeling in Adult Zebrafish Treated with Antimicrobials or Control |
| Study Summary | Sorbitol metabolism was traced with [U-13C]sorbitol in the intestine and liver of adult zebrafish with in-tact or depleted gut microbiota. We found that fish treated with antimicrobials had elevated sorbitol-derived carbon in metabolites in these organs. |
| Institute | Washington University in St. Louis |
| Last Name | Jackstadt |
| First Name | Madelyn |
| Address | One Brookings Drive, St. Louis, Missouri, 63130, USA |
| mjackstadt@wustl.edu | |
| Phone | 3149356405 |
| Submit Date | 2025-07-01 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-10-28 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| 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 |
Subject:
| Subject ID: | SU004222 |
| Subject Type: | Fish |
| Subject Species: | Danio rerio |
| Taxonomy ID: | 7955 |
Factors:
Subject type: Fish; Subject species: Danio rerio (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment | Sample source |
|---|---|---|---|
| SA473392 | USorbitol_Neg_Anti_06_Intestine | Antimicrobials | Intestine |
| SA473393 | USorbitol_Neg_Anti_02_Intestine | Antimicrobials | Intestine |
| SA473394 | USorbitol_Neg_Anti_01_Intestine | Antimicrobials | Intestine |
| SA473395 | USorbitol_Neg_Anti_04_Intestine | Antimicrobials | Intestine |
| SA473396 | USorbitol_Neg_Anti_03_Intestine | Antimicrobials | Intestine |
| SA473397 | USorbitol_Neg_Anti_06_Liver | Antimicrobials | Liver |
| SA473398 | USorbitol_Neg_Anti_04_Liver | Antimicrobials | Liver |
| SA473399 | USorbitol_Neg_Anti_02_Liver | Antimicrobials | Liver |
| SA473400 | USorbitol_Neg_Anti_03_Liver | Antimicrobials | Liver |
| SA473401 | USorbitol_Neg_Anti_01_Liver | Antimicrobials | Liver |
| SA473402 | USorbitol_Neg_Ctrl_12_Intestine | Control | Intestine |
| SA473403 | USorbitol_Neg_Ctrl_11_Intestine | Control | Intestine |
| SA473404 | USorbitol_Neg_Ctrl_10_Intestine | Control | Intestine |
| SA473405 | USorbitol_Neg_Ctrl_07_Intestine | Control | Intestine |
| SA473406 | USorbitol_Neg_Ctrl_09_Intestine | Control | Intestine |
| SA473407 | USorbitol_Neg_Ctrl_08_Intestine | Control | Intestine |
| SA473408 | USorbitol_Neg_Ctrl_07_Liver | Control | Liver |
| SA473409 | USorbitol_Neg_Ctrl_08_Liver | Control | Liver |
| SA473410 | USorbitol_Neg_Ctrl_09_Liver | Control | Liver |
| SA473411 | USorbitol_Neg_Ctrl_10_Liver | Control | Liver |
| SA473412 | USorbitol_Neg_Ctrl_11_Liver | Control | Liver |
| SA473413 | USorbitol_Neg_Ctrl_12_Liver | Control | Liver |
| Showing results 1 to 22 of 22 |
Collection:
| Collection ID: | CO004215 |
| Collection Summary: | Zebrafish were anesthetized and thoroughly dried before a scalpel was used to excise the caudal fin and some attached muscle tissue. Zebrafish were then immediately placed in a spin column such that blood from the wound could flow from the fish (in a 1.5 mL microcentrifuge tube with a small hole in the bottom) to a collection tube (a 0.5 mL microcentrifuge tube) during a brief, low-speed centrifugation (40 g for 1 min at 15 C). Immediately following blood collection, whole blood was placed on ice for 10 min while organs were harvested in pre-weighed microcentrifuge tubes and snap frozen in liquid nitrogen. After clotting on ice, whole blood was centrifuged at 1600 g for 10 min at 4 C. Serum (top layer) was then pipetted into a new 0.5 mL microcentrifuge tube and snap frozen in liquid nitrogen. |
| Sample Type: | intestine, liver |
Treatment:
| Treatment ID: | TR004231 |
| Treatment Summary: | For control treatment, conditioned facility water was autoclaved prior to zebrafish exposure. For antimicrobial treatment, 2% penicillin/streptomycin, 5 ug/mL kanamycin, 100 ug/mL ampicillin, and 250 ng/mL amphotericin b were added to autoclaved facility water. Both conditions were exposed to 0.1 mg/mL [U-13C]sorbitol. |
Sample Preparation:
| Sampleprep ID: | SP004228 |
| Sampleprep Summary: | For organ samples, tissues were ground in collection tubes by using a pestle while submerged in liquid nitrogen. Frozen samples in tubes were then massed, and the preweight of the tube was subtracted to yield tissue weight. 40 uL of 2:2:1 methanol:acetonitrile:water were added per mg wet tissue weight, and the sample was vortexed before snap freezing in liquid nitrogen. Simultaneously, samples were extracted by thawing in room temperature water (~10 s), sonicating (5 min), vortexing (~30 s), snap freezing in liquid nitrogen (~1 min), thawing in room temperature water (~10 s), sonicating (5 min), and vortexing (~30 s) before incubating at -20 C for 1 h. Following incubation, samples were centrifuged at 20,000 g for 10 min at 4 C, and supernatant was transferred to LC-MS vials for analysis. |
Chromatography:
| Chromatography ID: | CH005127 |
| Instrument Name: | Thermo Vanquish |
| Column Name: | HILICON iHILIC-(P) Classic (100 x 2.1mm,5um) |
| Column Temperature: | 40 |
| Flow Gradient: | 0-0.5 min, 90% solvent B at 200 μL/min; 0.5-17.5 min, linear gradient from 90% solvent B to 45% solvent B at 200 μL/min; 17.5-19 min, from 45% solvent B to 30% solvent B at 200 μL/min; 19-19.5 min, held at 30% solvent B at 200 μL/min; 19.5-22 min, from 30% solvent B to 90% solvent B at 200 μL/min; 22-23 min, 90% solvent B at 400 μL/min; 23-31.5 min, held at 90% solvent B at 400 μL/min; 31.5-32.5 min, ramped down to 90% solvent B at 200 μL/min; 32.5-34 min, held at 90% solvent B at 200 μL/min |
| Flow Rate: | 0-22 min, 200 μL/min; 22-31.5 min, 400 μL/min; 31.5-34 min, 200 μL/min |
| Solvent A: | 95% water/5% acetonitrile; 20 mM ammonium acetate; 0.1% ammonium hydroxide; 5 μM medronic acid |
| Solvent B: | 95% acetonitrile/5% water |
| Chromatography Type: | HILIC |
Analysis:
| Analysis ID: | AN006746 |
| Analysis Type: | MS |
| Chromatography ID: | CH005127 |
| Num Factors: | 4 |
| Num Metabolites: | 45 |
| Units: | Labeling Percentage |
