Summary of Study ST001991

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 PR001265. The data can be accessed directly via it's Project DOI: 10.21228/M86D99 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 IDST001991
Study TitleDynamics of bile acid metabolism between the host and gut microbiome in progression to islet autoimmunity (Blood)
Study SummaryPrevious studies suggest that the human gut microbiome is dysregulated in islet autoimmunity, preceding the clinical onset of type 1 diabetes (T1D). The Gut microbiota of the gut plays an important role in the regulation of bile acid (BA) metabolism. However, not much is known about the regulation of BAs during progression to T1D. Here, we analyzed BAs in a longitudinal series of serum (n= 333) and stool (n= 304) samples, collected at 3, 6, 12, 18, 24 and 36 months of age, from children who developed a single islet autoantibody (P1Ab), multiple islet autoantibodies (P2Ab), and controls (CTRs) who remained autoantibody (AAb) negative during the follow-up. In addition, we analyzed the stool microbiome by shotgun metagenomics in a subgroup of these children (n=111). Factor analysis showed that age had the strongest impact on BA and microbiome profiles. We found that, at an early age, the systemic BA (including taurine and glycine conjugates) and microbial secondary BA pathways were altered in the P2Ab group as compared to the P1Ab or CTR groups. Our findings thus suggest that dysregulated BA metabolism in early life may contribute to the risk and pathogenesis of T1D.
Institute
University of Turku
DepartmentUniversity of Turku
LaboratoryTurku Metabolomics Center
Last NameLamichhane
First NameSantosh
AddressYo Kylä 30A 6
Emailsantosh.lamichhane@utu.fi
Phone0452299070
Submit Date2021-11-01
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2023-01-31
Release Version1
Santosh Lamichhane Santosh Lamichhane
https://dx.doi.org/10.21228/M86D99
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001265
Project DOI:doi: 10.21228/M86D99
Project Title:Dynamics of bile acid metabolism between the host and gut microbiome in progression to islet autoimmunity
Project Type:MS analysis
Project Summary:Here, we analyzed BAs in a longitudinal series of serum (n= 333) collected at 3, 6, 12, 18, 24 and 36 months of age, from children who developed a single islet autoantibody (P1Ab), multiple islet autoantibodies (P2Ab), and controls (CTRs) who remained autoantibody (AAb) negative during the follow-up.
Institute:University of Turku
Department:University of Turku
Laboratory:Turku Metabolomics Center
Last Name:Lamichhane
First Name:Santosh
Address:Yo Kylä 30A 5
Email:santosh.lamichhane@utu.fi
Phone:0452299070
Funding Source:Academy of Finland postdoctoral grant (No. 323171 to S.L.), the Novo Nordisk Foundation (Grant no. NNF20OC0063971 to T.H. and M.O.)
Project Comments:Part 1 Serum data for DIABIMMUNE study. Please put this study and Data track ID into one project 2930.
Contributors:Santosh Lamichhane, Partho Sen, Alex M. Dickens, Marina Amaral Alves, Taina Härkönen, Jarno Honkanen, Tommi Vatanen, Ramnik J. Xavier, Tuulia Hyötyläinen, Mikael Knip4,, Matej Oresic

Subject:

Subject ID:SU002072
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Gender:Male and female

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Age sex Case
SA186025500116412 1 CTR
SA186026500117812 1 CTR
SA186027500112712 1 CTR
SA186028500118712 1 CTR
SA186029500110812 1 CTR
SA186030500088812 1 CTR
SA186031500093312 1 CTR
SA186032500135412 1 CTR
SA186033500288412 1 CTR
SA186034500418612 1 CTR
SA186035500419512 1 CTR
SA186036500419712 1 CTR
SA186037500408812 1 CTR
SA186038500408512 1 CTR
SA186039500072212 1 CTR
SA186040500400612 1 CTR
SA186041500275412 1 CTR
SA186042500254912 1 CTR
SA186043500033612 1 CTR
SA186044500038112 1 CTR
SA186045500117412 1 P1Ab
SA186046500282812 1 P1Ab
SA186047500256612 1 P1Ab
SA186048500129312 1 P1Ab
SA186049500131812 1 P1Ab
SA186050500140112 1 P1Ab
SA186051500415512 1 P1Ab
SA186052500409512 1 P1Ab
SA186053500428512 1 P1Ab
SA186054500038812 1 P1Ab
SA186055500071812 1 P1Ab
SA186056500086712 1 P1Ab
SA186057500083912 1 P1Ab
SA186058500437912 1 P1Ab
SA186059500136212 1 P2Ab
SA186060500114512 1 P2Ab
SA186061500415812 1 P2Ab
SA186062500407512 1 P2Ab
SA186063500292312 1 P2Ab
SA186064500410212 1 P2Ab
SA186065500030612 1 P2Ab
SA186066500272112 2 CTR
SA186067500430312 2 CTR
SA186068500433412 2 CTR
SA186069500563912 2 CTR
SA186070500422912 2 CTR
SA186071500416612 2 CTR
SA186072500270812 2 CTR
SA186073500080012 2 CTR
SA186074500293112 2 CTR
SA186075500124012 2 CTR
SA186076500260812 2 CTR
SA186077500555212 2 P1Ab
SA186078500418912 2 P1Ab
SA186079500115912 2 P1Ab
SA186080500081912 2 P1Ab
SA186081500260112 2 P1Ab
SA186082500429212 2 P1Ab
SA186083500432312 2 P2Ab
SA186084500258612 2 P2Ab
SA186085500251712 2 P2Ab
SA186086500420712 2 P2Ab
SA186087500432418 1 CTR
SA186088500136118 1 CTR
SA186089500576818 1 CTR
SA186090500438618 1 CTR
SA186091500130218 1 CTR
SA186092500039618 1 CTR
SA186093500553818 1 CTR
SA186094500130818 1 CTR
SA186095500565218 1 CTR
SA186096500029118 1 CTR
SA186097500557718 1 CTR
SA186098500440018 1 CTR
SA186099500137318 1 CTR
SA186100500097518 1 CTR
SA186101500145918 1 CTR
SA186102500143318 1 CTR
SA186103500296018 1 CTR
SA186104500288818 1 CTR
SA186105500414318 1 CTR
SA186106500150418 1 CTR
SA186107500292018 1 P1Ab
SA186108500152418 1 P1Ab
SA186109500156218 1 P1Ab
SA186110500441618 1 P1Ab
SA186111500568218 1 P1Ab
SA186112500147218 1 P1Ab
SA186113500129518 1 P1Ab
SA186114500136518 1 P1Ab
SA186115500554818 1 P1Ab
SA186116500405118 1 P1Ab
SA186117500109318 1 P1Ab
SA186118500146218 1 P1Ab
SA186119500417018 1 P1Ab
SA186120500297518 1 P2Ab
SA186121500416218 1 P2Ab
SA186122500443018 1 P2Ab
SA186123500439018 1 P2Ab
SA186124500133618 1 P2Ab
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Collection:

Collection ID:CO002065
Collection Summary:The DIABIMMUNE study recruited 832 families in Finland (Espoo), Estonia (Tartu), and Russia (Petrozavodsk) with infants carrying HLA alleles that conferred risk for autoimmunity. The subjects involved in the current study were chosen from the subset (n = 74) of international DIABIMMUNE study children who progressed to at least a single AAb (P1Ab, n = 23), who progressed to multiple islet AAb (P2Ab, n = 13), and controls (CTRs, n = 38), i.e. the children who remained islet AAb- negative during the follow-up in a longitudinal series of samples collected at 3, 6, 12, 18, 24 and 36 months from each child (Kostic et al. 2015). The study groups were matched for HLA-associated diabetes risk, sex, country and period of birth. This study was conducted according to the guidelines in the Declaration of Helsinki. The Ethics and Research Committee of the participating Universities and Hospitals approved the study protocol. All families provided written informed consent prior to sample collection.
Sample Type:Blood (serum)
Storage Conditions:-80℃

Treatment:

Treatment ID:TR002084
Treatment Summary:The bile acids were measured in serum and fecal sample as described previously (Jäntti et al., 2014; Salihović et al., 2020).

Sample Preparation:

Sampleprep ID:SP002078
Sampleprep Summary:Briefly, 20 μL of serum (prepared by adding 1:20 (m/v) ultrapure water to 50 mg of feces) was filtered through a Ostro Protein Precipitation and Phospholipid Removal 96-well plate (Waters Corporation, Milford, USA), using 100 μL of cold methanol contemning the internal standard mixtures (LCA-d4, TCA-d4, GUDCA-d4, GCA-d4, CA-d4, UDCA-d4, GCDCA-d4, CDCA-d4, DCA-d4, GLCA-d4). The eluent was collected and evaporated to dryness and the residue was re-suspended in 20 μL of a 40:60 MeOH: H2O v/v mixture. The analyses were performed on an ACQUITY HSS T3 (2.1×100 mm, 1.8 μm) column, Waters (Milford), coupled to a triple quadrupole mass spectrometer (Waters Corporation, Milford, USA) with an atmospheric electrospray interface operating in negative ion mode. Separation was performed using gradient elution with 0.1 % formic acid in water (v/v) (A) and 0.1 % formic acid in acetonitrile:methanol (3:1, v/v) (B) at a flow rate of 0.5 mL/ min. Gradient program was 0 min 15 % B, 0-1 min; 30 % B, 1- 16 min; 16-18 min; 70 % B, 18–23 min 100 % B, and equilibrium time between runs was 7 min. The injection volume was 5 μL and the column was kept at 35 °C. An external calibration with nine calibration points (0.0025–600 ng/mL) was carried out for use in quantitation.

Combined analysis:

Analysis ID AN003248
Analysis type MS
Chromatography type Reversed phase
Chromatography system Waters
Column Waters ACQUITY UPLC HSS T3 (100 x 2.1mm,1.8um)
MS Type ESI
MS instrument type Triple quadrupole
MS instrument name ABI Sciex 5500 QTrap
Ion Mode NEGATIVE
Units ng/ml

Chromatography:

Chromatography ID:CH002393
Chromatography Summary:The analyses were performed on an ACQUITY HSS T3 (2.1×100 mm, 1.8 μm) column, Waters (Milford), coupled to a triple quadrupole mass spectrometer (Waters Corporation, Milford, USA) with an atmospheric electrospray interface operating in negative ion mode. Separation was performed using gradient elution with 0.1 % formic acid in water (v/v) (A) and 0.1 % formic acid in acetonitrile:methanol (3:1, v/v) (B) at a flow rate of 0.5 mL/ min. Gradient program was 0 min 15 % B, 0-1 min; 30 % B, 1- 16 min; 16-18 min; 70 % B, 18–23 min 100 % B, and equilibrium time between runs was 7 min. The injection volume was 5 μL and the column was kept at 35 °C.
Instrument Name:Waters
Column Name:Waters ACQUITY UPLC HSS T3 (100 x 2.1mm,1.8um)
Column Temperature:35
Flow Gradient:0 min 15 % B, 0-1 min; 30 % B, 1- 16 min; 16-18 min; 70 % B, 18–23 min 100 % B, and equilibrium time between runs was 7 min.
Flow Rate:0.5 mL/min
Solvent A:100% water; 0.1% formic acid
Solvent B:75% acetonitrile/25% methanol; 0.1% formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS003021
Analysis ID:AN003248
Instrument Name:ABI Sciex 5500 QTrap
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:The bile acids were measured in serum and fecal sample as described based on . 20 μL of serum, using the same internal standard mixtures, was filtered through a frit filter plate (96-Well Protein Precipitation Filter Plate, Sigma Aldrich), and the effluent was collected and evaporated to dryness and the residue was dissolved in 20 μL of a 40:60 MeOH: H2O v/v mixture containing the same injection standards. Analyses were performed on an ACQUITY UPLC system coupled to a triple quadrupole mass spectrometer (Waters Corporation, Milford, USA) with an atmospheric electrospray interface operating in negative ion mode. An external calibration with six calibration points (0.5–600 ng/mL), including a solvent blank, was carried out for use in quantitation.
Ion Mode:NEGATIVE
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