Summary of Study ST003140

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 PR001952. The data can be accessed directly via it's Project DOI: 10.21228/M8DD95 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.

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Study IDST003140
Study TitleUntargeted metabolomic analysis of lumenal contents from AMX-treated and untreated mice
Study SummaryAntibiotics cause collateral damage to resident microbes that is associated with various health risks. To-date, studies have largely focused on impacts of antibiotics on large intestinal and fecal microbiota. Here, we employ a GI-wide integrated multiomic approach to reveal that amoxicillin (AMX) treatment reduces overall bacterial abundance, bile salt hydrolase activity and unconjugated bile acids in the small intestine (SI). An accompanying loss of fatty acids and increase in acyl-carnitines in the large intestine corresponded with spatially-distinct expansions of proteobacteria. Parasutterella excrementihominis utilized fatty acid biosynthesis, becoming dominant in the SI while multiple Klebsiella species employed fatty acid oxidation during expansion in the large intestine. Depletion of bile acids and lipids may contribute to AMX-induced dysbiosis in the lower GI. To test this, we demonstrate that restoration of unconjugated bile acids can mitigate losses of commensals in the large intestine while also inhibiting the expansion of Proteobacteria during AMX treatment. NOTE: This study does not include results for Blood. They are in the companion study.
Institute
Brown University
Last NameBeekman
First NameChapman
AddressBMC 613, 171 Meeting Street, Providence RI 02912
EmailChapman_Beekman@brown.edu
Phone4012071832
Submit Date2024-01-17
Num Groups2
Total Subjects12
Num Females12
Analysis Type DetailLC-MS
Release Date2024-08-05
Release Version1
Chapman Beekman Chapman Beekman
https://dx.doi.org/10.21228/M8DD95
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001952
Project DOI:doi: 10.21228/M8DD95
Project Title:Spatial analysis of murine GI reveals role of small intestinal bile acid metabolism in amoxicillin-induced dysbiosis
Project Summary:Antibiotics cause collateral damage to resident microbes that is associated with various health risks. To-date, studies have largely focused on impacts of antibiotics on large intestinal and fecal microbiota. Here, we employ a GI-wide integrated multiomic approach to reveal that amoxicillin (AMX) treatment reduces overall bacterial abundance, bile salt hydrolase activity and unconjugated bile acids in the small intestine (SI). An accompanying loss of fatty acids and increase in acyl-carnitines in the large intestine corresponded with spatially-distinct expansions of proteobacteria. Parasutterella excrementihominis utilized fatty acid biosynthesis, becoming dominant in the SI while multiple Klebsiella species employed fatty acid oxidation during expansion in the large intestine. Depletion of bile acids and lipids may contribute to AMX-induced dysbiosis in the lower GI. To test this, we demonstrate that restoration of unconjugated bile acids can mitigate losses of commensals in the large intestine while also inhibiting the expansion of Proteobacteria during AMX treatment.
Institute:Brown University
Department:MMI
Laboratory:MMI, Belenky Lab
Last Name:Beekman
First Name:Chapman
Address:BMC 613, 171 Meeting Street, Providence RI 02912
Email:Chapman_Beekman@brown.edu
Phone:4012071832

Subject:

Subject ID:SU003257
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:C57/BL6
Animal Animal Supplier:JAX

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Treatment Sample source
SA340522CB81Amox Blood
SA340523CB80Amox Blood
SA340524CB74Amox Blood
SA340525CB73Amox Blood
SA340526CB75Amox Blood
SA340527CB79Amox Blood
SA340528CB5Amox Cecum
SA340529CB17Amox Cecum
SA340530CB41Amox Cecum
SA340531CB11Amox Cecum
SA340532CB47Amox Cecum
SA340533CB53Amox Cecum
SA340534CB18Amox Colon
SA340535CB48Amox Colon
SA340536CB12Amox Colon
SA340537CB42Amox Colon
SA340538CB6Amox Colon
SA340539CB54Amox Colon
SA340540CB46Amox DSI
SA340541CB52Amox DSI
SA340542CB40Amox DSI
SA340543CB10Amox DSI
SA340544CB4Amox DSI
SA340545CB16Amox DSI
SA340546CB3Amox MSI
SA340547CB9Amox MSI
SA340548CB45Amox MSI
SA340549CB39Amox MSI
SA340550CB15Amox MSI
SA340551CB51Amox MSI
SA340552CB38Amox PSI
SA340553CB44Amox PSI
SA340554CB2Amox PSI
SA340555CB14Amox PSI
SA340556CB8Amox PSI
SA340557CB50Amox PSI
SA340558CB49Amox Stomach
SA340559CB1Amox Stomach
SA340560CB43Amox Stomach
SA340561CB13Amox Stomach
SA340562CB37Amox Stomach
SA340563CB7Amox Stomach
SA340564CB76Control Blood
SA340565CB78Control Blood
SA340566CB77Control Blood
SA340567CB83Control Blood
SA340568CB84Control Blood
SA340569CB82Control Blood
SA340570CB23Control Cecum
SA340571CB29Control Cecum
SA340572CB65Control Cecum
SA340573CB71Control Cecum
SA340574CB59Control Cecum
SA340575CB35Control Cecum
SA340576CB60Control Colon
SA340577CB72Control Colon
SA340578CB66Control Colon
SA340579CB24Control Colon
SA340580CB30Control Colon
SA340581CB36Control Colon
SA340582CB28Control DSI
SA340583CB34Control DSI
SA340584CB64Control DSI
SA340585CB22Control DSI
SA340586CB70Control DSI
SA340587CB58Control DSI
SA340588CB21Control MSI
SA340589CB63Control MSI
SA340590CB27Control MSI
SA340591CB69Control MSI
SA340592CB57Control MSI
SA340593CB33Control MSI
SA340594CB20Control PSI
SA340595CB68Control PSI
SA340596CB56Control PSI
SA340597CB26Control PSI
SA340598CB62Control PSI
SA340599CB32Control PSI
SA340600CB31Control Stomach
SA340601CB55Control Stomach
SA340602CB67Control Stomach
SA340603CB61Control Stomach
SA340604CB25Control Stomach
SA340605CB19Control Stomach
Showing results 1 to 84 of 84

Collection:

Collection ID:CO003250
Collection Summary:Lumenal contents collected from multiple GI sites and immediately flash frozen in liquid nitrogen
Sample Type:Intestine

Treatment:

Treatment ID:TR003266
Treatment Summary:Mice were treated for 24h with amoxicillin/vehicle in drinking water
Treatment Compound:Amoxicillin
Treatment Route:oral
Animal Endp Euthanasia:isoflurane, cervical dislocation

Sample Preparation:

Sampleprep ID:SP003264
Sampleprep Summary:Frozen lumenal contents were lyophilized and 10mg of dry contents were extracted twice in 300µL in (2:1) acetone and isopropanol. Samples were maintained on dry ice during extraction steps. Extracts were diluted 1:10 in a solution of 80% methanol in water. All solvents were LC-MS grade purchased from Fisher Scientific

Combined analysis:

Analysis ID AN005153
Analysis type MS
Chromatography type None (Direct infusion)
Chromatography system None
Column none
MS Type ESI
MS instrument type QTOF
MS instrument name Agilent 6550 QTOF
Ion Mode NEGATIVE
Units ion counts

Chromatography:

Chromatography ID:CH003901
Instrument Name:None
Column Name:none
Column Temperature:na
Flow Gradient:none
Flow Rate:na
Solvent A:none
Solvent B:none
Chromatography Type:None (Direct infusion)

MS:

MS ID:MS004889
Analysis ID:AN005153
Instrument Name:Agilent 6550 QTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:A pooled study sample (pSS) was prepared by combining 5 µL of each sample. The pSS was injected every ten samples during data acquisition. Instrumental Analysis Metabolome profiles of the sample extracts were acquired using flow-injection mass spectrometry. The method described here is adapted from Fuhrer et al 2011. The instrumentation consisted of an Agilent 6550 iFunnel LC-MS Q-TOF mass spectrometer in tandem with an MPS3 autosampler (Gerstel) and an Agilent 1260 Infinity II quaternary pump. The running buffer was 60% isopropanol in water (v/v) with 1 mM ammonium fluoride. Hexakis (1H, 1H, 3H-tetrafluoropropoxy)-phosphazene) (Agilent) and 3-amino-1-propanesulfonic acid (HOT) (Sigma Aldrich) were added to the running buffer to serve as lockmasses. The isocratic flow rate was set to 0.150 mL/min. The instrument was run in 4GHz High Resolution, negative ionization mode. Mass spectra between 50 and 1,000 m/z were collected in profile mode. 5 µL of each sample were injected twice, consecutively, within 0.96 minutes to serve as technical replicates. The pooled study sample was injected periodically throughout the batch. Data Processing & Annotation Raw profile data were centroided, merged, and recalibrated using MATLAB software described by Fuhrer et al (10.1021/ac201267k).
Ion Mode:NEGATIVE
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