Summary of Study ST001992

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 IDST001992
Study TitleDynamics of bile acid metabolism between the host and gut microbiome in progression to islet autoimmunity (Feces)
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 Date2021-11-15
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:SU002073
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 Agemonths Case sex
SA186358310756612 CTR 1
SA186359310367512 CTR 1
SA186360310528612 CTR 1
SA186361310361012 CTR 1
SA186362310376012 CTR 1
SA186363311384412 CTR 1
SA186364311385812 CTR 1
SA186365310328112 CTR 1
SA186366310335112 CTR 1
SA186367310791612 CTR 1
SA186368311384112 CTR 1
SA186369310727912 CTR 1
SA186370310119512 CTR 1
SA186371310792512 CTR 1
SA186372310612412 CTR 1
SA186373310931812 CTR 1
SA186374310904812 CTR 1
SA186375310549012 CTR 1
SA186376310565012 CTR 1
SA186377310606312 CTR 2
SA186378310604612 CTR 2
SA186379310580012 CTR 2
SA186380311398312 CTR 2
SA186381311230212 CTR 2
SA186382310240512 CTR 2
SA186383311460012 CTR 2
SA186384311441412 CTR 2
SA186385311440212 CTR 2
SA186386311376412 CTR 2
SA186387310964312 P1Ab 1
SA186388311368612 P1Ab 1
SA186389310518312 P1Ab 1
SA186390311370312 P1Ab 1
SA186391310366012 P1Ab 1
SA186392311429512 P1Ab 1
SA186393310798012 P1Ab 1
SA186394311705412 P1Ab 1
SA186395310948612 P1Ab 1
SA186396310120412 P1Ab 1
SA186397311949612 P1Ab 1
SA186398311670112 P1Ab 1
SA186399310781112 P1Ab 1
SA186400311464712 P1Ab 1
SA186401311453412 P1Ab 2
SA186402310579212 P1Ab 2
SA186403311199712 P1Ab 2
SA186404311379412 P1Ab 2
SA186405310496212 P1Ab 2
SA186406311196512 P2Ab 1
SA186407311383112 P2Ab 1
SA186408310788912 P2Ab 1
SA186409311211712 P2Ab 1
SA186410311724512 P2Ab 1
SA186411310349712 P2Ab 1
SA186412310394112 P2Ab 1
SA186413311454512 P2Ab 2
SA186414310785912 P2Ab 2
SA186415310764712 P2Ab 2
SA186416311216618 CTR 1
SA186417310385918 CTR 1
SA186418311200418 CTR 1
SA186419311468118 CTR 1
SA186420311652318 CTR 1
SA186421310941618 CTR 1
SA186422311455118 CTR 1
SA186423310853718 CTR 1
SA186424311232718 CTR 1
SA186425310959818 CTR 1
SA186426311469018 CTR 1
SA186427310954618 CTR 1
SA186428311702818 CTR 1
SA186429311687218 CTR 1
SA186430310745118 CTR 1
SA186431311727718 CTR 1
SA186432310208318 CTR 1
SA186433310729618 CTR 1
SA186434310849918 CTR 2
SA186435310902718 CTR 2
SA186436310764118 CTR 2
SA186437311234318 CTR 2
SA186438311258618 CTR 2
SA186439311234918 CTR 2
SA186440311346418 CTR 2
SA186441311278118 CTR 2
SA186442311359118 CTR 2
SA186443311362418 CTR 2
SA186444311376718 CTR 2
SA186445311271418 CTR 2
SA186446311732818 CTR 2
SA186447311200318 P1Ab 1
SA186448311249918 P1Ab 1
SA186449310319918 P1Ab 1
SA186450311962218 P1Ab 1
SA186451311992518 P1Ab 1
SA186452310808718 P1Ab 1
SA186453311705318 P1Ab 1
SA186454311237318 P1Ab 1
SA186455311739718 P1Ab 1
SA186456310952018 P1Ab 1
SA186457310739618 P1Ab 1
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Collection:

Collection ID:CO002066
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:Feces
Storage Conditions:-80℃

Treatment:

Treatment ID:TR002085
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:SP002079
Sampleprep Summary:Briefly,fecal homogenate (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 AN003249
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:CH002394
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:MS003022
Analysis ID:AN003249
Instrument Name:ABI Sciex 5500 QTrap
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:The bile acids were measured in 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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