Summary of Study ST003508

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 PR002154. The data can be accessed directly via it's Project DOI: 10.21228/M8681W 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 IDST003508
Study TitleAssociations Between Maternal Microbiome, Metabolome and Incidence of Low Birth Weight in Guatemalan Participants from the Women First Trial
Study SummaryLow birth weight (babies born at less than 2,500 grams) affects approximately 15 to 20 percent of global births annually and is associated with poor child development. The goal of this study was to examine relationships between maternal microbial taxa, fecal metabolites, and maternal anthropometry on incidence of LBW in resource-limited settings. This was a secondary analysis of the Women First trial conducted in a semi-rural region of Guatemala. Maternal weight was measured at 12 and 34 weeks (wk) of gestation. Infant anthropometry measures were collected within 48 h of delivery. Maternal fecal samples at 12 and 34 wk were used for microbiome (16S rRNA gene amplicon sequencing) and metabolomics analysis (34 wk only). Linear mixed models using the MaAslin2 package were utilized to assess changes in microbiome associated with LBW. Predictive models using gradient boosted machines (XGBoost) were developed using the H2o.ai engine. No differences in β-diversity were observed at either time point between mothers with LBW infants relative to normal weight (NW) infants. Simpson diversity at 12 and 34 wk was lower in mothers with LBW infants. Notable differences in genus-level abundance between LBW and NW mothers (p< 0.05) were observed at 12 weeks with increasing abundances of Barnesiella, Faecalibacterium, Sutterella, and Bacterioides. At 34 weeks, there were lower abundances of Magasphaera, Phascolarctobacterium, and Turicibacter and higher abundances of Bacteriodes, and Fusobacterium in mothers with LBW infants. Fecal metabolites related to bile acids, tryptophan metabolism and fatty acid related metabolites changed in mothers with LBW infants. Classification models to predict LBW based on maternal anthropometry and predicted microbial functions showed moderate performance. Collectively, the findings indicate that less beneficial gut microbes and circulating metabolites of the mother is associated with low birth weight infants compared to normal weight. Future research should target functional and predictive roles of the maternal gut microbiome in infant birth outcomes including birthweight.
Institute
Arkansas Children's Nutrition Center
DepartmentPediatrics
LaboratoryMetabolomics and Analytical Chemistry Core
Last NameLan
First NameRenny
Address108 Holland Lane
Emailslan@uams.edu
Phone9196073272
Submit Date2024-09-07
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2024-10-21
Release Version1
Renny Lan Renny Lan
https://dx.doi.org/10.21228/M8681W
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR002154
Project DOI:doi: 10.21228/M8681W
Project Title:Associations Between Maternal Microbiome, Metabolome and Incidence of Low-Birth Weight in Guatemalan Participants from the Women First Trial
Project Summary:Low birth weight (babies born at less than 2,500 grams) affects approximately 15 to 20 percent of global births annually and is associated with poor child development. The goal of this study was to examine relationships between maternal microbial taxa, fecal metabolites, and maternal anthropometry on incidence of LBW in resource-limited settings. This was a secondary analysis of the Women First trial conducted in a semi-rural region of Guatemala. Maternal weight was measured at 12 and 34 weeks (wk) of gestation. Infant anthropometry measures were collected within 48 h of delivery. Maternal fecal samples at 12 and 34 wk were used for microbiome (16S rRNA gene amplicon sequencing) and metabolomics analysis (34 wk only). Linear mixed models using the MaAslin2 package were utilized to assess changes in microbiome associated with LBW. Predictive models using gradient boosted machines (XGBoost) were developed using the H2o.ai engine. No differences in β-diversity were observed at either time point between mothers with LBW infants relative to normal weight (NW) infants. Simpson diversity at 12 and 34 wk was lower in mothers with LBW infants. Notable differences in genus-level abundance between LBW and NW mothers (p< 0.05) were observed at 12 weeks with increasing abundances of Barnesiella, Faecalibacterium, Sutterella, and Bacterioides. At 34 weeks, there were lower abundances of Magasphaera, Phascolarctobacterium, and Turicibacter and higher abundances of Bacteriodes, and Fusobacterium in mothers with LBW infants. Fecal metabolites related to bile acids, tryptophan metabolism and fatty acid related metabolites changed in mothers with LBW infants. Classification models to predict LBW based on maternal anthropometry and predicted microbial functions showed moderate performance. Collectively, the findings indicate that less beneficial gut microbes and circulating metabolites of the mother is associated with low birth weight infants compared to normal weight. Future research should target functional and predictive roles of the maternal gut microbiome in infant birth outcomes including birthweight.
Institute:Arkansas Children's Nutrition Center
Department:Pediatrics
Laboratory:Metabolomics and Analytical Chemistry Core
Last Name:Lan
First Name:Renny
Address:15 Children's Way
Email:slan@uams.edu
Phone:5013642813

Subject:

Subject ID:SU003637
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

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

mb_sample_id local_sample_id Sample source Low Birth Weight status status Treatment Arm
SA386021QC10Feces n/a n/a
SA386022QC11Feces n/a n/a
SA386023QC12Feces n/a n/a
SA386024QC13Feces n/a n/a
SA386025QC9Feces n/a n/a
SA386026F21Feces no Arm1
SA385984F40Feces No Arm1
SA385985F38Feces No Arm1
SA385986F37Feces No Arm1
SA385987F34Feces No Arm1
SA385988F33Feces No Arm1
SA385989F2Feces No Arm1
SA385990F29Feces No Arm1
SA385991F28Feces No Arm1
SA386027F20Feces no Arm2
SA385992F25Feces No Arm2
SA385993F13Feces No Arm2
SA385994F15Feces No Arm2
SA385995F23Feces No Arm2
SA385996F6Feces No Arm3
SA385997F39Feces No Arm3
SA385998F27Feces No Arm3
SA385999F30Feces No Arm3
SA386000F18Feces No Arm3
SA386001F11Feces No Arm3
SA386002F16Feces Yes Arm1
SA386003F22Feces Yes Arm1
SA386004F3Feces Yes Arm1
SA386005F10Feces Yes Arm1
SA386006F31Feces Yes Arm1
SA386007F32Feces Yes Arm1
SA386008F19Feces Yes Arm1
SA386009F12Feces Yes Arm1
SA386028F7Feces yes Arm2
SA386010F1Feces Yes Arm2
SA386011F9Feces Yes Arm2
SA386012F8Feces Yes Arm2
SA386013F4Feces Yes Arm2
SA386014F14Feces Yes Arm2
SA386015F26Feces Yes Arm2
SA386016F17Feces Yes Arm2
SA386017F36Feces Yes Arm2
SA386018F5Feces Yes Arm3
SA386019F35Feces Yes Arm3
SA386020F24Feces Yes Arm3
SA386029Process BlankWater n/a n/a
Showing results 1 to 46 of 46

Collection:

Collection ID:CO003630
Collection Summary:Fecal samples were collected at 34 weeks gestation (Arms 1, 2, and 3). Arm 1 received a daily small-quantity lipid-based micronutrient supplement (sqLNS) starting at 3 months before conception and throughout pregnancy, Arm 2 received daily sqLNS supplementation starting at 12 weeks of gestation and through the remainder of pregnancy, and Arm 3 received only the local standard of care which included iron and folate supplementation. Stool was collected into fecal bags using a sterile scoop and placed into a Styrofoam container with ice or ice packs. The research team picked up samples the day of stool passage, transferred samples back to facility where they were aliquoted into storage tubes. Samples were stored at -80° C until analyses.
Sample Type:Feces

Treatment:

Treatment ID:TR003646
Treatment Summary:This is a secondary analysis of the Women First: Preconception Maternal Intervention Nutrition Trial (ClinicalTrials.gov ID: NCT01883193, (Hambidge et al. 2019; DOI: 10.1093/ajcn/nqy228)). Only participants recruited from Chimaltenango, Guatemala were included in the study. The full study details can be found in previous publications (Hambidge et al 2019, DOI: 10.1093/ajcn/nqy228, Tang et al, 2022, DOI: 10.3389/fmicb.2022.823757). Briefly, participants were randomized into three different treatment arms: Arm 1 received a daily small-quantity lipid-based micronutrient supplement (sqLNS) starting at ≥ 3 months before conception and throughout pregnancy, Arm 2 received daily sqLNS supplementation starting at 12 weeks of gestation and through the remainder of pregnancy, and Arm 3 received only the local standard of care which typically included iron and folate supplementation (Figure 1A). All participants recruited for this study were between 16-35 years old, parity 0-5, and planned to conceive during the following 18 months. Written informed consent was obtained from all the participants. Study protocol was approved by Institutional Review Board at the University of Colorado and Comité de Ética de la Universidad Francisco Marroquín.

Sample Preparation:

Sampleprep ID:SP003644
Sampleprep Summary:Approximately 100 mg of wet stool samples at 34 weeks LBW and NW group, were extracted and subjected to untargeted metabolomics analyses using liquid chromatography/mass spectrometry (LC-MS) at the Metabolomics and Analytical Chemistry Core at Arkansas Children’s Nutrition Center. Briefly, 500 µL of LC-MS grade 50% of MeOH in water and 1 ml of Acetonitrile was added to the stool. The mixture was quantitatively transferred to screw cap tube containing 200 µl of 1.44 mm beads, 100 µL of 0.5 mm beads and 3 beads of 2.8 mm beads. Samples were homogenized with a Precellys 24 two cycles, 30 secs each at 5300 rpm. . The mixture was vortexed for 10 min at 4 °C on a ThermoMixer (Eppendorf Inc., Enfield, CT) and then centrifuged at 4,347x g at 4 °C for 10 min (Centrifuge 5910 Ri, Eppendorf Inc., Enfield, CT). 700 µL of the supernatant was aliquoted and subsequently dried by using a vacuum concentrator (SpeedVac SPD210, Thermo Fisher Scientific Waltham, MA). Extracts were then reconstituted in 250μL of 5% methanol spiked with 1000 ng mL-1 sulfadimethoxine (SDMO) for immediate instrumental analysis. Pooled quality control (QC) samples were prepared by pooling equal volumes of each sample extract (50 µl).
Sampleprep Protocol ID:Meghan_et_al_Sample_Preparation_Chromatography_and_Mass_Spectrometry_conditions.pdf

Combined analysis:

Analysis ID AN005761 AN005762
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Thermo Vanquish Thermo Vanquish
Column Acquity Premier CSH C18 (100 x 2.1 mm, 1.7 um) Acquity Premier CSH C18 (100 x 2.1 mm, 1.7 um)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Orbitrap Exploris 480 Thermo Orbitrap Exploris 480
Ion Mode POSITIVE NEGATIVE
Units Peak area Peak area

Chromatography:

Chromatography ID:CH004373
Chromatography Summary:An Orbitrap Exploris 480 mass spectrometer (ThermoFisher Scientific, Waltham, MA) interfaced with the Vanquish UHPLC system and fitted with high flow and low flow heat-electrospray ionization (HESI) probes was used for instrumental analysis. A flow rate of 0.3 mL min–1 was employed to carry out chromatographic separations using an Acquity Premier CSH C18 1.7 μm × 2.1 × 100 mm Column (Waters, USA). Water (A) and acetonitrile (B), both acidified with 0.1% formic acid, made up the mobile phase system. The LC gradient was set to 0 min, 0% B; 2 min, 40% B; 8 min, 98% B; 10 min, 98% B; 10.5 min, 0% B; 15 min, 0% B. Throughout the analysis, a 40 °C column temperature and a 5.0 μL injection volume were employed.
Methods Filename:Meghan_et_al_Sample_Preparation_Chromatography_and_Mass_Spectrometry_conditions.pdf
Instrument Name:Thermo Vanquish
Column Name:Acquity Premier CSH C18 (100 x 2.1 mm, 1.7 um)
Column Temperature:40 °C
Flow Gradient:The LC gradient was set to 0 min, 0% B; 2 min, 40% B; 8 min, 98% B; 10 min, 98% B; 10.5 min, 0% B; 15 min, 0% B.
Flow Rate:0.3 mL/min
Solvent A:100% water; 0.1% formic acid
Solvent B:100% acetonitrile; 0.1% formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS005483
Analysis ID:AN005761
Instrument Name:Thermo Orbitrap Exploris 480
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:The samples were analysed in both positive and negative ionization mode. The electrospray ionization voltage was kept at 3.6 kV in the positive mode. Sheath gas was set to 35, auxiliary gas was set at 10, and sweep gas was set to 1 arbitrary unit (Arb). The ion transfer tube temperature (ITT) was set at 350°C and the vaporizer temperature was set at 350°C. The scan parameters for the mass spectrometer included 6 s chromatogram peak width and a 15-min duration time in DDA mode. Full MS1 used the Orbitrap mass analyzer with a resolution of 180,000, scan range (m/z) of 60–900 in positive mode and 58-870 in negative mode, maximum injection time (MIT) of 100, automatic gain control (AGC) target of 5e5, 1 microscan, and RF lens set to 70. MS/MS analysis was performed on the pooled QC samples using six rounds of iterative DDA (ThermoFisher AcquireX) at a resolution of 30,000 FWH using a stepped HCD collision energies of 20, 40, and 60 V. Other MS/MS parameters included: MIT of 50 ms, microscan set to 1, AGC set to 1e6, and a scan range of 60–900 in positive mode and 58-870 in negative mode. The top 5 abundant precursors within an isolation window of 2 m/z were chosen for MS/MS analysis. Xcalibur v4.4.16.14 (ThermoFisher Scientific, Waltham, MA) was used for instrument control and data acquisition.
Ion Mode:POSITIVE
Analysis Protocol File:Meghan_et_al_Sample_Preparation_Chromatography_and_Mass_Spectrometry_conditions.pdf
  
MS ID:MS005484
Analysis ID:AN005762
Instrument Name:Thermo Orbitrap Exploris 480
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:The samples were analysed in both positive and negative ionization mode. The electrospray ionization voltage was kept at 3.5 kV in the negative mode. Sheath gas was set to 35, auxiliary gas was set at 10, and sweep gas was set to 1 arbitrary unit (Arb). The ion transfer tube temperature (ITT) was set at 350°C and the vaporizer temperature was set at 350°C. The scan parameters for the mass spectrometer included 6 s chromatogram peak width and a 15-min duration time in DDA mode. Full MS1 used the Orbitrap mass analyzer with a resolution of 180,000, scan range (m/z) of 60–900 in positive mode and 58-870 in negative mode, maximum injection time (MIT) of 100, automatic gain control (AGC) target of 5e5, 1 microscan, and RF lens set to 70. MS/MS analysis was performed on the pooled QC samples using six rounds of iterative DDA (ThermoFisher AcquireX) at a resolution of 30,000 FWH using a stepped HCD collision energies of 20, 40, and 60 V. Other MS/MS parameters included: MIT of 50 ms, microscan set to 1, AGC set to 1e6, and a scan range of 60–900 in positive mode and 58-870 in negative mode. The top 5 abundant precursors within an isolation window of 2 m/z were chosen for MS/MS analysis. Xcalibur v4.4.16.14 (ThermoFisher Scientific, Waltham, MA) was used for instrument control and data acquisition.
Ion Mode:NEGATIVE
Analysis Protocol File:Meghan_et_al_Sample_Preparation_Chromatography_and_Mass_Spectrometry_conditions.pdf
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