#METABOLOMICS WORKBENCH rennylan_20240907_125332 DATATRACK_ID:5179 STUDY_ID:ST003508 ANALYSIS_ID:AN005761 PROJECT_ID:PR002154 VERSION 1 CREATED_ON October 2, 2024, 7:01 pm #PROJECT PR:PROJECT_TITLE Associations Between Maternal Microbiome, Metabolome and Incidence of Low-Birth PR:PROJECT_TITLE Weight in Guatemalan Participants from the Women First Trial PR:PROJECT_SUMMARY Low birth weight (babies born at less than 2,500 grams) affects approximately 15 PR:PROJECT_SUMMARY to 20 percent of global births annually and is associated with poor child PR:PROJECT_SUMMARY development. The goal of this study was to examine relationships between PR:PROJECT_SUMMARY maternal microbial taxa, fecal metabolites, and maternal anthropometry on PR:PROJECT_SUMMARY incidence of LBW in resource-limited settings. This was a secondary analysis of PR:PROJECT_SUMMARY the Women First trial conducted in a semi-rural region of Guatemala. Maternal PR:PROJECT_SUMMARY weight was measured at 12 and 34 weeks (wk) of gestation. Infant anthropometry PR:PROJECT_SUMMARY measures were collected within 48 h of delivery. Maternal fecal samples at 12 PR:PROJECT_SUMMARY and 34 wk were used for microbiome (16S rRNA gene amplicon sequencing) and PR:PROJECT_SUMMARY metabolomics analysis (34 wk only). Linear mixed models using the MaAslin2 PR:PROJECT_SUMMARY package were utilized to assess changes in microbiome associated with LBW. PR:PROJECT_SUMMARY Predictive models using gradient boosted machines (XGBoost) were developed using PR:PROJECT_SUMMARY the H2o.ai engine. No differences in β-diversity were observed at either time PR:PROJECT_SUMMARY point between mothers with LBW infants relative to normal weight (NW) infants. PR:PROJECT_SUMMARY Simpson diversity at 12 and 34 wk was lower in mothers with LBW infants. Notable PR:PROJECT_SUMMARY differences in genus-level abundance between LBW and NW mothers (p< 0.05) were PR:PROJECT_SUMMARY observed at 12 weeks with increasing abundances of Barnesiella, PR:PROJECT_SUMMARY Faecalibacterium, Sutterella, and Bacterioides. At 34 weeks, there were lower PR:PROJECT_SUMMARY abundances of Magasphaera, Phascolarctobacterium, and Turicibacter and higher PR:PROJECT_SUMMARY abundances of Bacteriodes, and Fusobacterium in mothers with LBW infants. Fecal PR:PROJECT_SUMMARY metabolites related to bile acids, tryptophan metabolism and fatty acid related PR:PROJECT_SUMMARY metabolites changed in mothers with LBW infants. Classification models to PR:PROJECT_SUMMARY predict LBW based on maternal anthropometry and predicted microbial functions PR:PROJECT_SUMMARY showed moderate performance. Collectively, the findings indicate that less PR:PROJECT_SUMMARY beneficial gut microbes and circulating metabolites of the mother is associated PR:PROJECT_SUMMARY with low birth weight infants compared to normal weight. Future research should PR:PROJECT_SUMMARY target functional and predictive roles of the maternal gut microbiome in infant PR:PROJECT_SUMMARY birth outcomes including birthweight. PR:INSTITUTE Arkansas Children's Nutrition Center PR:DEPARTMENT Pediatrics PR:LABORATORY Metabolomics and Analytical Chemistry Core PR:LAST_NAME Lan PR:FIRST_NAME Renny PR:ADDRESS 15 Children's Way PR:EMAIL slan@uams.edu PR:PHONE 5013642813 #STUDY ST:STUDY_TITLE Associations Between Maternal Microbiome, Metabolome and Incidence of Low Birth ST:STUDY_TITLE Weight in Guatemalan Participants from the Women First Trial ST:STUDY_SUMMARY Low birth weight (babies born at less than 2,500 grams) affects approximately 15 ST:STUDY_SUMMARY to 20 percent of global births annually and is associated with poor child ST:STUDY_SUMMARY development. The goal of this study was to examine relationships between ST:STUDY_SUMMARY maternal microbial taxa, fecal metabolites, and maternal anthropometry on ST:STUDY_SUMMARY incidence of LBW in resource-limited settings. This was a secondary analysis of ST:STUDY_SUMMARY the Women First trial conducted in a semi-rural region of Guatemala. Maternal ST:STUDY_SUMMARY weight was measured at 12 and 34 weeks (wk) of gestation. Infant anthropometry ST:STUDY_SUMMARY measures were collected within 48 h of delivery. Maternal fecal samples at 12 ST:STUDY_SUMMARY and 34 wk were used for microbiome (16S rRNA gene amplicon sequencing) and ST:STUDY_SUMMARY metabolomics analysis (34 wk only). Linear mixed models using the MaAslin2 ST:STUDY_SUMMARY package were utilized to assess changes in microbiome associated with LBW. ST:STUDY_SUMMARY Predictive models using gradient boosted machines (XGBoost) were developed using ST:STUDY_SUMMARY the H2o.ai engine. No differences in β-diversity were observed at either time ST:STUDY_SUMMARY point between mothers with LBW infants relative to normal weight (NW) infants. ST:STUDY_SUMMARY Simpson diversity at 12 and 34 wk was lower in mothers with LBW infants. Notable ST:STUDY_SUMMARY differences in genus-level abundance between LBW and NW mothers (p< 0.05) were ST:STUDY_SUMMARY observed at 12 weeks with increasing abundances of Barnesiella, ST:STUDY_SUMMARY Faecalibacterium, Sutterella, and Bacterioides. At 34 weeks, there were lower ST:STUDY_SUMMARY abundances of Magasphaera, Phascolarctobacterium, and Turicibacter and higher ST:STUDY_SUMMARY abundances of Bacteriodes, and Fusobacterium in mothers with LBW infants. Fecal ST:STUDY_SUMMARY metabolites related to bile acids, tryptophan metabolism and fatty acid related ST:STUDY_SUMMARY metabolites changed in mothers with LBW infants. Classification models to ST:STUDY_SUMMARY predict LBW based on maternal anthropometry and predicted microbial functions ST:STUDY_SUMMARY showed moderate performance. Collectively, the findings indicate that less ST:STUDY_SUMMARY beneficial gut microbes and circulating metabolites of the mother is associated ST:STUDY_SUMMARY with low birth weight infants compared to normal weight. Future research should ST:STUDY_SUMMARY target functional and predictive roles of the maternal gut microbiome in infant ST:STUDY_SUMMARY birth outcomes including birthweight. ST:INSTITUTE Arkansas Children's Nutrition Center ST:DEPARTMENT Pediatrics ST:LABORATORY Metabolomics and Analytical Chemistry Core ST:LAST_NAME Lan ST:FIRST_NAME Renny ST:ADDRESS 108 Holland Lane ST:EMAIL slan@uams.edu ST:PHONE 9196073272 #SUBJECT SU:SUBJECT_TYPE Human SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 #FACTORS #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data SUBJECT_SAMPLE_FACTORS 626020B F1 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm2 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_20B_F1_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_20B_F1_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 631970P F10 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm1 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_70P_F10_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_70P_F10_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 673530J F11 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm3 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_30J_F11_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_30J_F11_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 642110I F12 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm1 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_10I_F12_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_10I_F12_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 626620A F13 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm2 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_20A_F13_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_20A_F13_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 615680Q F14 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm2 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_80Q_F14_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_80Q_F14_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 615950N F15 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm2 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_50N_F15_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_50N_F15_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 615970H F16 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm1 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_70H_F16_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_70H_F16_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 600950V F17 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm2 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_50V_F17_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_50V_F17_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 662990J F18 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm3 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_90J_F18_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_90J_F18_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 667770V F19 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm1 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_70V_F19_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_70V_F19_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 663170T F2 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm1 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_70T_F2_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_70T_F2_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 601280M F20 Sample source:Feces | Low Birth Weight status status:no | Treatment Arm:Arm2 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_80M_F20_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_80M_F20_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 606140D F21 Sample source:Feces | Low Birth Weight status status:no | Treatment Arm:Arm1 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_40D_F21_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_40D_F21_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 626540V F22 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm1 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_40V_F22_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_40V_F22_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 600920H F23 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm2 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_20H_F23_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_20H_F23_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 631930E F24 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm3 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_30E_F24_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_30E_F24_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 600220M F25 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm2 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_20M_F25_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_20M_F25_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 693680B F26 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm2 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_80B_F26_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_80B_F26_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 616360G F27 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm3 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_60G_F27_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_60G_F27_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 663040J F28 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm1 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_40J_F28_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_40J_F28_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 616170L F29 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm1 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_70L_F29_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_70L_F29_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 663010S F3 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm1 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_10S_F3_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_10S_F3_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 641730G F30 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm3 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_30G_F30_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_30G_F30_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 606170R F31 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm1 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_70R_F31_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_70R_F31_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 610870N F32 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm1 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_70N_F32_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_70N_F32_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 610440P F33 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm1 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_40P_F33_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_40P_F33_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 672940S F34 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm1 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_40S_F34_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_40S_F34_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 652160K F35 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm3 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_60K_F35_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_60K_F35_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 653080D F36 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm2 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_80D_F36_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_80D_F36_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 668010Q F37 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm1 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_10Q_F37_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_10Q_F37_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 626840J F38 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm1 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_40J_F38_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_40J_F38_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 663090R F39 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm3 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_90R_F39_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_90R_F39_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 653880R F4 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm2 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_80R_F4_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_80R_F4_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 636410F F40 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm1 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_10F_F40_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_10F_F40_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 653760E F5 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm3 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_60E_F5_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_60E_F5_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 663060D F6 Sample source:Feces | Low Birth Weight status status:No | Treatment Arm:Arm3 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_60D_F6_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_60D_F6_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 606150A F7 Sample source:Feces | Low Birth Weight status status:yes | Treatment Arm:Arm2 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_50A_F7_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_50A_F7_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 663080U F8 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm2 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_80U_F8_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_80U_F8_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS 641950P F9 Sample source:Feces | Low Birth Weight status status:Yes | Treatment Arm:Arm2 RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_50P_F9_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_50P_F9_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS n/a Process Blank Sample source:Water | Low Birth Weight status status:n/a | Treatment Arm:n/a RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_Reagent_Blank_pos_02_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_Reagent_Blank_Neg_02_20220725.raw SUBJECT_SAMPLE_FACTORS n/a QC10 Sample source:Feces | Low Birth Weight status status:n/a | Treatment Arm:n/a RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_Pool_QC10_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_Pool_QC10_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS n/a QC11 Sample source:Feces | Low Birth Weight status status:n/a | Treatment Arm:n/a RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_Pool_QC11_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_Pool_QC11_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS n/a QC12 Sample source:Feces | Low Birth Weight status status:n/a | Treatment Arm:n/a RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_Pool_QC12_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_Pool_QC12_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS n/a QC13 Sample source:Feces | Low Birth Weight status status:n/a | Treatment Arm:n/a RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_Pool_QC13_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_Pool_QC13_Neg_20220725.raw SUBJECT_SAMPLE_FACTORS n/a QC9 Sample source:Feces | Low Birth Weight status status:n/a | Treatment Arm:n/a RAW_FILE_NAME(Raw data file name_Positive)=Laxmi_Pool_QC9_Pos_20220725.raw; RAW_FILE_NAME(Raw data file name_Negative)=Laxmi_Pool_QC9_Neg_20220725.raw #COLLECTION CO:COLLECTION_SUMMARY Fecal samples were collected at 34 weeks gestation (Arms 1, 2, and 3). Arm 1 CO:COLLECTION_SUMMARY received a daily small-quantity lipid-based micronutrient supplement (sqLNS) CO:COLLECTION_SUMMARY starting at 3 months before conception and throughout pregnancy, Arm 2 received CO:COLLECTION_SUMMARY daily sqLNS supplementation starting at 12 weeks of gestation and through the CO:COLLECTION_SUMMARY remainder of pregnancy, and Arm 3 received only the local standard of care which CO:COLLECTION_SUMMARY included iron and folate supplementation. Stool was collected into fecal bags CO:COLLECTION_SUMMARY using a sterile scoop and placed into a Styrofoam container with ice or ice CO:COLLECTION_SUMMARY packs. The research team picked up samples the day of stool passage, transferred CO:COLLECTION_SUMMARY samples back to facility where they were aliquoted into storage tubes. Samples CO:COLLECTION_SUMMARY were stored at -80° C until analyses. CO:SAMPLE_TYPE Feces #TREATMENT TR:TREATMENT_SUMMARY This is a secondary analysis of the Women First: Preconception Maternal TR:TREATMENT_SUMMARY Intervention Nutrition Trial (ClinicalTrials.gov ID: NCT01883193, (Hambidge et TR:TREATMENT_SUMMARY al. 2019; DOI: 10.1093/ajcn/nqy228)). Only participants recruited from TR:TREATMENT_SUMMARY Chimaltenango, Guatemala were included in the study. The full study details can TR:TREATMENT_SUMMARY be found in previous publications (Hambidge et al 2019, DOI: TR:TREATMENT_SUMMARY 10.1093/ajcn/nqy228, Tang et al, 2022, DOI: 10.3389/fmicb.2022.823757). Briefly, TR:TREATMENT_SUMMARY participants were randomized into three different treatment arms: Arm 1 received TR:TREATMENT_SUMMARY a daily small-quantity lipid-based micronutrient supplement (sqLNS) starting at TR:TREATMENT_SUMMARY ≥ 3 months before conception and throughout pregnancy, Arm 2 received daily TR:TREATMENT_SUMMARY sqLNS supplementation starting at 12 weeks of gestation and through the TR:TREATMENT_SUMMARY remainder of pregnancy, and Arm 3 received only the local standard of care which TR:TREATMENT_SUMMARY typically included iron and folate supplementation (Figure 1A). All participants TR:TREATMENT_SUMMARY recruited for this study were between 16-35 years old, parity 0-5, and planned TR:TREATMENT_SUMMARY to conceive during the following 18 months. Written informed consent was TR:TREATMENT_SUMMARY obtained from all the participants. Study protocol was approved by Institutional TR:TREATMENT_SUMMARY Review Board at the University of Colorado and Comité de Ética de la TR:TREATMENT_SUMMARY Universidad Francisco Marroquín. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Approximately 100 mg of wet stool samples at 34 weeks LBW and NW group, were SP:SAMPLEPREP_SUMMARY extracted and subjected to untargeted metabolomics analyses using liquid SP:SAMPLEPREP_SUMMARY chromatography/mass spectrometry (LC-MS) at the Metabolomics and Analytical SP:SAMPLEPREP_SUMMARY Chemistry Core at Arkansas Children’s Nutrition Center. Briefly, 500 µL of SP:SAMPLEPREP_SUMMARY LC-MS grade 50% of MeOH in water and 1 ml of Acetonitrile was added to the SP:SAMPLEPREP_SUMMARY stool. The mixture was quantitatively transferred to screw cap tube containing SP:SAMPLEPREP_SUMMARY 200 µl of 1.44 mm beads, 100 µL of 0.5 mm beads and 3 beads of 2.8 mm beads. SP:SAMPLEPREP_SUMMARY Samples were homogenized with a Precellys 24 two cycles, 30 secs each at 5300 SP:SAMPLEPREP_SUMMARY rpm. . The mixture was vortexed for 10 min at 4 °C on a ThermoMixer (Eppendorf SP:SAMPLEPREP_SUMMARY Inc., Enfield, CT) and then centrifuged at 4,347x g at 4 °C for 10 min SP:SAMPLEPREP_SUMMARY (Centrifuge 5910 Ri, Eppendorf Inc., Enfield, CT). 700 µL of the supernatant SP:SAMPLEPREP_SUMMARY was aliquoted and subsequently dried by using a vacuum concentrator (SpeedVac SP:SAMPLEPREP_SUMMARY SPD210, Thermo Fisher Scientific Waltham, MA). Extracts were then reconstituted SP:SAMPLEPREP_SUMMARY in 250μL of 5% methanol spiked with 1000 ng mL-1 sulfadimethoxine (SDMO) for SP:SAMPLEPREP_SUMMARY immediate instrumental analysis. Pooled quality control (QC) samples were SP:SAMPLEPREP_SUMMARY prepared by pooling equal volumes of each sample extract (50 µl). SP:SAMPLEPREP_PROTOCOL_ID Meghan_et_al_Sample_Preparation_Chromatography_and_Mass_Spectrometry_conditions.pdf #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY An Orbitrap Exploris 480 mass spectrometer (ThermoFisher Scientific, Waltham, CH:CHROMATOGRAPHY_SUMMARY MA) interfaced with the Vanquish UHPLC system and fitted with high flow and low CH:CHROMATOGRAPHY_SUMMARY flow heat-electrospray ionization (HESI) probes was used for instrumental CH:CHROMATOGRAPHY_SUMMARY analysis. A flow rate of 0.3 mL min–1 was employed to carry out CH:CHROMATOGRAPHY_SUMMARY chromatographic separations using an Acquity Premier CSH C18 1.7 μm × 2.1 × CH:CHROMATOGRAPHY_SUMMARY 100 mm Column (Waters, USA). Water (A) and acetonitrile (B), both acidified with CH:CHROMATOGRAPHY_SUMMARY 0.1% formic acid, made up the mobile phase system. The LC gradient was set to 0 CH:CHROMATOGRAPHY_SUMMARY min, 0% B; 2 min, 40% B; 8 min, 98% B; 10 min, 98% B; 10.5 min, 0% B; 15 min, 0% CH:CHROMATOGRAPHY_SUMMARY B. Throughout the analysis, a 40 °C column temperature and a 5.0 μL injection CH:CHROMATOGRAPHY_SUMMARY volume were employed. CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Thermo Vanquish CH:COLUMN_NAME Acquity Premier CSH C18 (100 x 2.1 mm, 1.7 um) CH:SOLVENT_A 100% water; 0.1% formic acid CH:SOLVENT_B 100% acetonitrile; 0.1% formic acid CH:FLOW_GRADIENT The LC gradient was set to 0 min, 0% B; 2 min, 40% B; 8 min, 98% B; 10 min, 98% CH:FLOW_GRADIENT B; 10.5 min, 0% B; 15 min, 0% B. CH:FLOW_RATE 0.3 mL/min CH:COLUMN_TEMPERATURE 40 °C CH:METHODS_FILENAME Meghan_et_al_Sample_Preparation_Chromatography_and_Mass_Spectrometry_conditions.pdf #ANALYSIS AN:ANALYSIS_TYPE MS AN:ANALYSIS_PROTOCOL_FILE Meghan_et_al_Sample_Preparation_Chromatography_and_Mass_Spectrometry_conditions.pdf #MS MS:INSTRUMENT_NAME Thermo Orbitrap Exploris 480 MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS The samples were analysed in both positive and negative ionization mode. The MS:MS_COMMENTS electrospray ionization voltage was kept at 3.6 kV in the positive mode. Sheath MS:MS_COMMENTS gas was set to 35, auxiliary gas was set at 10, and sweep gas was set to 1 MS:MS_COMMENTS arbitrary unit (Arb). The ion transfer tube temperature (ITT) was set at 350°C MS:MS_COMMENTS and the vaporizer temperature was set at 350°C. The scan parameters for the MS:MS_COMMENTS mass spectrometer included 6 s chromatogram peak width and a 15-min duration MS:MS_COMMENTS time in DDA mode. Full MS1 used the Orbitrap mass analyzer with a resolution of MS:MS_COMMENTS 180,000, scan range (m/z) of 60–900 in positive mode and 58-870 in negative MS:MS_COMMENTS mode, maximum injection time (MIT) of 100, automatic gain control (AGC) target MS:MS_COMMENTS of 5e5, 1 microscan, and RF lens set to 70. MS/MS analysis was performed on the MS:MS_COMMENTS pooled QC samples using six rounds of iterative DDA (ThermoFisher AcquireX) at a MS:MS_COMMENTS resolution of 30,000 FWH using a stepped HCD collision energies of 20, 40, and MS:MS_COMMENTS 60 V. Other MS/MS parameters included: MIT of 50 ms, microscan set to 1, AGC set MS:MS_COMMENTS to 1e6, and a scan range of 60–900 in positive mode and 58-870 in negative MS:MS_COMMENTS mode. The top 5 abundant precursors within an isolation window of 2 m/z were MS:MS_COMMENTS chosen for MS/MS analysis. Xcalibur v4.4.16.14 (ThermoFisher Scientific, MS:MS_COMMENTS Waltham, MA) was used for instrument control and data acquisition. MS:MS_RESULTS_FILE ST003508_AN005761_Results.txt UNITS:Peak area Has m/z:Yes Has RT:Yes RT units:Minutes #END