Summary of study ST001748

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 PR001120. The data can be accessed directly via it's Project DOI: 10.21228/M8XM6R 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 IDST001748
Study TitleRationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis
Study TypeTargeted metabolomics
Study SummaryGUT103 and GUT108, live biotherapeutic products rationally designed to complement missing or underrepresented functions in the dysbiotic microbiome of IBD patients; they address upstream targets, rather than targeting a single cytokine to block downstream inflammation responses. Systematic colonization experiments in colitis mouse models were performed to test their therapeutic effects. Targeted fecal metabolomics data uploaded here of bile acids, short-chain fatty acids, and tryptophan metabolites provides a unique metabolome perspective for evaluation of the therapeutic potential of GUT103 and GUT108.
Institute
University of North Carolina at Chapel Hill
LaboratoryGusto Global LLC.
Last NameLai
First NameYunjia
Address1104 MHRC, 135 Dauer Drive, Chapel Hill, NC 27599, USA
Emaillai7@live.unc.edu
Phone+1 919-480-5489
Submit Date2021-04-22
Num Groups12
PublicationsNature Communications
Raw Data AvailableYes
Raw Data File Type(s).mzXML
Analysis Type DetailGC/LC-MS
Release Date2021-04-30
Release Version1
Yunjia Lai Yunjia Lai
https://dx.doi.org/10.21228/M8XM6R
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001120
Project DOI:doi: 10.21228/M8XM6R
Project Title:Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis
Project Type:targeted metabolomics
Project Summary:Environmental factors, mucosal permeability and defective immunoregulation drive overactive immunity to a subset of resident intestinal bacteria that mediate multiple inflammatory conditions. GUT-103 and GUT-108, live biotherapeutic products rationally designed to complement missing or underrepresented functions in the dysbiotic microbiome of IBD patients, address upstream targets, rather than targeting a single cytokine to block downstream inflammation responses. GUT-103, composed of 17 strains that synergistically provide protective and sustained engraftment in the IBD inflammatory environment, prevented, and treated chronic immune-mediated colitis. Therapeutic application of GUT-108 reversed established colitis in a humanized chronic T cell-mediated mouse model. It decreased pathobionts while expanding resident protective bacteria; produced metabolites promoting mucosal healing and immunoregulatory responses; decreased inflammatory cytokines and Th-1 and Th-17 cells; and induced interleukin-10-producing colonic regulatory cells, and IL-10-independent homeostatic pathways. We propose GUT-108 for treating and preventing relapse for IBD and other inflammatory conditions characterized by unbalanced microbiota and mucosal permeability.
Institute:University of North Carolina at Chapel Hill
Department:UNC Departments of Medicine, Microbiology and Immunology, Center for Gastrointestinal Biology and Disease; UNC Department of Environmental Sciences and Engineering
Laboratory:R. Balfour Sartor Lab; Kun Lu Lab
Last Name:Lai
First Name:Yunjia
Address:1104 MHRC, 135 Dauer Drive, NC
Email:lai7@live.unc.edu
Phone:919-480-5489
Funding Source:Gusto Global LLC.; National Institute of Health (NIH) (grant no. P40OD010995; P30DK034987; P01DK094779); the Crohn’s and Colitis Foundation
Publications:Nature Communications

Subject:

Subject ID:SU001825
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:GF 129SvEv background IL-10-deficient mice (Il10-/-); Il10-eGFP-reporter (Il10+/eGFP) mice (on a C57BL/6J background)
Age Or Age Range:8-12 week old
Animal Animal Supplier:8-12 week-age GF 129SvEv background IL-10-deficient mice (Il10-/-) were obtained from University of North Carolina National Gnotobiotic Rodent Resource Center; Il10-eGFP-reporter (Il10+/eGFP) mice on a C57BL/6J background mice were originally provided by Dr. C. L. Karp (Global Health, Bill & Melinda Gates Foundation, USA)
Animal Housing:Germ-free and gnotobiotic conditions at National Gnotobiotic Rodent Resource Center, University of North Carolina

Factors:

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

mb_sample_id local_sample_id Treatment
SA163498bileacid_Exp2_15_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163499bileacid_Exp2_14_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163500bileacid_Exp2_12_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163501bileacid_Exp2_16_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163502bileacid_Exp2_13_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163503bileacid_Exp2_18_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163504bileacid_Exp2_22_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163505bileacid_Exp2_20_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163506bileacid_Exp2_19_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163507bileacid_Exp2_11_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163508bileacid_Exp2_17_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163509bileacid_Exp2_10_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163510bileacid_Exp2_4_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163511bileacid_Exp2_3_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163512bileacid_Exp2_2_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163513bileacid_Exp2_1_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163514bileacid_Exp2_5_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163515bileacid_Exp2_6_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163516bileacid_Exp2_9_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163517bileacid_Exp2_8_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163518bileacid_Exp2_7_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163519scfa_Exp2_22_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163520scfa_Exp2_21_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163521scfa_Exp2_6_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163522scfa_Exp2_7_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163523scfa_Exp2_8_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163524scfa_Exp2_9_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163525scfa_Exp2_5_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163526scfa_Exp2_4_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163527scfa_Exp2_1_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163528scfa_Exp2_2_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163529scfa_Exp2_3_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163530scfa_Exp2_10_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163531scfa_Exp2_11_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163532scfa_Exp2_17_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163533scfa_Exp2_18_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163534scfa_Exp2_19_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163535scfa_Exp2_20_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163536scfa_Exp2_16_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163537scfa_Exp2_15_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163538scfa_Exp2_12_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163539scfa_Exp2_13_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163540scfa_Exp2_14_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163541trps_Exp2_1_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163542bileacid_Exp2_21_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163543trps_Exp2_13_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163544trps_Exp2_14_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163545trps_Exp2_12_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163546trps_Exp2_11_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163547trps_Exp2_10_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163548trps_Exp2_15_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163549trps_Exp2_16_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163550trps_Exp2_21_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163551trps_Exp2_22_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163552trps_Exp2_20_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163553trps_Exp2_19_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163554trps_Exp2_17_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163555trps_Exp2_9_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163556trps_Exp2_18_Hu+GUT108_week4After 2 wk GUT/PBS therapy
SA163557trps_Exp2_2_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163558trps_Exp2_8_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163559trps_Exp2_4_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163560trps_Exp2_3_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163561trps_Exp2_7_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163562trps_Exp2_5_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163563trps_Exp2_6_Hu+PBS_week4After 2 wk GUT/PBS therapy
SA163564scfa_Exp3_14_GUT108_week2After GUT108/PBS therapy
SA163565scfa_Exp3_6_PBS_week2After GUT108/PBS therapy
SA163566scfa_Exp3_4_PBS_week2After GUT108/PBS therapy
SA163567scfa_Exp3_15_GUT108_week2After GUT108/PBS therapy
SA163568scfa_Exp3_5_PBS_week2After GUT108/PBS therapy
SA163569scfa_Exp3_20_GUT108_week2After GUT108/PBS therapy
SA163570bileacid_Exp3_19_GUT108_week2After GUT108/PBS therapy
SA163571bileacid_Exp3_18_GUT108_week2After GUT108/PBS therapy
SA163572scfa_Exp3_3_PBS_week2After GUT108/PBS therapy
SA163573scfa_Exp3_19_GUT108_week2After GUT108/PBS therapy
SA163574scfa_Exp3_18_GUT108_week2After GUT108/PBS therapy
SA163575scfa_Exp3_17_GUT108_week2After GUT108/PBS therapy
SA163576trps_Exp3_5_PBS_week2After GUT108/PBS therapy
SA163577trps_Exp3_18_GUT108_week2After GUT108/PBS therapy
SA163578trps_Exp3_19_GUT108_week2After GUT108/PBS therapy
SA163579trps_Exp3_17_GUT108_week2After GUT108/PBS therapy
SA163580bileacid_Exp3_17_GUT108_week2After GUT108/PBS therapy
SA163581trps_Exp3_15_GUT108_week2After GUT108/PBS therapy
SA163582trps_Exp3_14_GUT108_week2After GUT108/PBS therapy
SA163583trps_Exp3_20_GUT108_week2After GUT108/PBS therapy
SA163584trps_Exp3_1_PBS_week2After GUT108/PBS therapy
SA163585trps_Exp3_3_PBS_week2After GUT108/PBS therapy
SA163586trps_Exp3_4_PBS_week2After GUT108/PBS therapy
SA163587trps_Exp3_6_PBS_week2After GUT108/PBS therapy
SA163588scfa_Exp3_1_PBS_week2After GUT108/PBS therapy
SA163589bileacid_Exp3_20_GUT108_week2After GUT108/PBS therapy
SA163590bileacid_Exp3_5_PBS_week2After GUT108/PBS therapy
SA163591bileacid_Exp3_4_PBS_week2After GUT108/PBS therapy
SA163592bileacid_Exp3_3_PBS_week2After GUT108/PBS therapy
SA163593bileacid_Exp3_1_PBS_week2After GUT108/PBS therapy
SA163594bileacid_Exp3_15_GUT108_week2After GUT108/PBS therapy
SA163595bileacid_Exp3_6_PBS_week2After GUT108/PBS therapy
SA163596bileacid_Exp3_14_GUT108_week2After GUT108/PBS therapy
SA163597trps_Exp3_15_GUT108_week0Before GUT108/PBS therapy (baseline)
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Collection:

Collection ID:CO001818
Collection Summary:For samples for targeted metabolomics analysis, mouse cecal content and/or feces were collected.
Collection Protocol ID:University of North Carolina at Chapel Hill Institutional Animal Care and Use Committee (18-266.0-B)
Sample Type:Feces
Storage Conditions:-80℃

Treatment:

Treatment ID:TR001838
Treatment Summary:For treatment 200 µl of diluted human donor stool was applied by oral gavage on day 1 to Il10-/- mice. The stool was derived from a single healthy donor, Donor-Y, and was previously found to induce moderate to severe colitis in Il10-/- mice. One gram stool was diluted 100- fold with anaerobic PBS, and vigorously mixed for 5 minutes under anaerobic conditions. For application of GUT-103 and GUT-108, 300µl resuspended strain mixture in anaerobic PBS was applied per mouse by oral gavage. GUT-103 and GUT-108 strains were grown individually, subsequently mixed to equal concentrations (cfu/ml), and provided at a dose of 2.0x10+7 cfu/strain in a total volume of 300 µl. The strain mixture was provided four times via oral gavage on days 15, 17, 22 and 25 (Il10-/- mice) or on days 1, 3, 8 and 11 (Il10+/eGFP mice).

Sample Preparation:

Sampleprep ID:SP001831
Sampleprep Summary:Bile acids, SCFAs, and tryptophan metabolites were extracted (with careful cleanup or derivatization procedures whenever necessary) and analyzed using mass spectrometry-based platforms.
Sampleprep Protocol Filename:Protocols.pdf
Processing Storage Conditions:On ice
Extraction Method:Bile acid: SPE and LLE; SCFA: alkaline aqueous extraction; tryptophan metabolites: 1:1 MeOH:Water LLE
Extract Cleanup:For Bile acids, C18 solid-phase extraction cleanup and concentration was used.
Extract Storage:-80℃
Sample Derivatization:For SCFAs, propyl chloroformate derivatization was performed.

Combined analysis:

Analysis ID AN002845 AN002846 AN002847
Analysis type MS MS MS
Chromatography type GC Reversed phase Reversed phase
Chromatography system Agilent 7820A Thermo Vanquish Thermo Vanquish
Column Agilent DB5-MS (30m x 0.25mm, 0.25um) Waters Acquity BEH HSS T3 (100 x 2.1mm, 1.8um) Waters Acquity BEH C18 (150 x 2mm, 1.7um)
MS Type EI ESI ESI
MS instrument type Single quadrupole Orbitrap Triple quadrupole
MS instrument name Agilent 5977B Thermo Q Exactive Orbitrap Thermo Quantis QQQ
Ion Mode POSITIVE POSITIVE NEGATIVE
Units μmol/kg ng/g mg/g

Chromatography:

Chromatography ID:CH002106
Chromatography Summary:Generic DB-5ms GC capillary column for analysis of SCFA derivatives.
Instrument Name:Agilent 7820A
Column Name:Agilent DB5-MS (30m x 0.25mm, 0.25um)
Chromatography Type:GC
  
Chromatography ID:CH002107
Chromatography Summary:C18 LC (HSS-T3) for quantitation of tryptophan metabolites
Instrument Name:Thermo Vanquish
Column Name:Waters Acquity BEH HSS T3 (100 x 2.1mm, 1.8um)
Chromatography Type:Reversed phase
  
Chromatography ID:CH002108
Chromatography Summary:C18 LC (BEH C18) and (HSS T3) for quantitation of bile acids
Instrument Name:Thermo Vanquish
Column Name:Waters Acquity BEH C18 (150 x 2mm, 1.7um)
Chromatography Type:Reversed phase

MS:

MS ID:MS002638
Analysis ID:AN002845
Instrument Name:Agilent 5977B
Instrument Type:Single quadrupole
MS Type:EI
MS Comments:fullscan data with scan range of m/z 30-600; Peak integration was performed in MassHunter Qual.
Ion Mode:POSITIVE
  
MS ID:MS002639
Analysis ID:AN002846
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Optimized PRM method scanning characteristic MS2 fragment ion for absolute quantitation.
Ion Mode:POSITIVE
  
MS ID:MS002640
Analysis ID:AN002847
Instrument Name:Thermo Quantis QQQ
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:Optimized SRM method scanning characteristic MS2 fragment ion for absolute quantitation.
Ion Mode:NEGATIVE
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