scholarly journals Longitudinal Plasma Metabolomics Profile in Pregnancy—A Study in an Ethnically Diverse U.S. Pregnancy Cohort

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3080
Author(s):  
Susanna D. Mitro ◽  
Jing Wu ◽  
Mohammad L. Rahman ◽  
Yaqi Cao ◽  
Yeyi Zhu ◽  
...  
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Multiple Testing ◽  
Ethnically Diverse ◽  
Multiple Testing Correction ◽  
Fetal Sex ◽  
Longitudinal Measurements ◽  
Longitudinal Plasma ◽  
Race Ethnicity ◽  
In Pregnancy

Amino acids, fatty acids, and acylcarnitine metabolites play a pivotal role in maternal and fetal health, but profiles of these metabolites over pregnancy are not completely established. We described longitudinal trajectories of targeted amino acids, fatty acids, and acylcarnitines in pregnancy. We quantified 102 metabolites and combinations (37 fatty acids, 37 amino acids, and 28 acylcarnitines) in plasma samples from pregnant women in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies—Singletons cohort (n = 214 women at 10–14 and 15–26 weeks, 107 at 26–31 weeks, and 103 at 33–39 weeks). We used linear mixed models to estimate metabolite trajectories and examined variation by body mass index (BMI), race/ethnicity, and fetal sex. After excluding largely undetected metabolites, we analyzed 77 metabolites and combinations. Levels of 13 of 15 acylcarnitines, 7 of 25 amino acids, and 18 of 37 fatty acids significantly declined over gestation, while 8 of 25 amino acids and 10 of 37 fatty acids significantly increased. Several trajectories appeared to differ by BMI, race/ethnicity, and fetal sex although no tests for interactions remained significant after multiple testing correction. Future studies merit longitudinal measurements to capture metabolite changes in pregnancy, and larger samples to examine modifying effects of maternal and fetal characteristics.

scholarly journals Longitudinal Metabolomic Profile Trajectories in Healthy Pregnancy and Variation by BMI and Fetal Sex

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1041-1041
Author(s):  
Susanna D Mitro ◽  
Jing Wu ◽  
Mohammad Rahman ◽  
Mengying Li ◽  
Stefanie Hinkle ◽  
...  
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Normal Pregnancy ◽  
Maternal Plasma ◽  
Plasma Metabolites ◽  
Maternal Body Mass Index ◽  
Fetal Sex ◽  
Funding Sources ◽  
Branched Chain ◽  
Maternal Bmi

Abstract Objectives Maternal plasma metabolites have been linked with pregnancy outcomes, and two studies reported that metabolite levels differ by trimester. However, dynamic metabolite trajectories in normal pregnancy have not been characterized. We examined metabolite trajectories and tested whether trajectories differed by maternal body mass index (BMI) or fetal sex. Methods We quantified 3 panels of targeted metabolites—37 amino acids, 37 phospholipid fatty acids and 28 acylcarnitines—in blood samples collected longitudinally from 214 pregnant women (at 10–14, 15–26, 26–31, and 33–39 weeks, staggered to sample most weeks of pregnancy). Participants were healthy controls in a nested case-control study in the Fetal Growth Studies—Singletons. We used linear mixed models to estimate metabolite trajectories and evaluate if trajectories varied by maternal BMI (<25, 25–29.9, 30) or fetal sex. We used novel methods such as hierarchical clustering to group metabolite trajectories. Results Concentrations of most carnitines, 57% of fatty acids, and 24% of amino acids (e.g., branched chain amino acids) significantly decreased over pregnancy; 22% of fatty acids and 24% of amino acids (e.g., threonine, histidine) significantly increased. Trajectories of 2 carnitines (propionylcarnitine and stearoylcarnitine) and 3 fatty acids (15:0, 17:0, 22:0) significantly differed by sex. Trajectories of dodecenoylcarnitine, 2 fatty acids and 2 fatty acid ratios (17:0, 20:3n6, AA/DHA, AA/(DHA + EPA)) significantly differed by BMI: specifically, 17:0, AA/DHA, and AA/(DHA + EPA) decreased less over pregnancy for women with high BMI. Conclusions Concentrations of most metabolites significantly changed during pregnancy, and trajectories of some carnitines and fatty acids differed significantly by maternal BMI and fetal sex. Future pregnancy metabolomics studies should consider BMI, fetal sex, and multiple samples across pregnancy. Funding Sources Eunice Kennedy Shriver National Institute of Child Health and Human Development.

1010-P: Effects of MEDI0382, an Oxyntomodulin-Like Peptide with Targeted GLP-1/Glucagon Receptor Activity, on Amino Acids, Ketones, and Free Fatty Acids

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1010-P
Author(s):  
VICTORIA E. PARKER ◽  
DARREN ROBERTSON ◽  
TAO WANG ◽  
DAVID C. HORNIGOLD ◽  
MAXIMILIAN G. POSCH ◽  
...  
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Receptor Activity ◽  
Glucagon Receptor

Gastrointestinal Interaction between Dietary Amino Acids and Gut Microbiota: With Special Emphasis on Host Nutrition

2020 ◽  
Vol 21 (8) ◽  
pp. 785-798 ◽  
Author(s):  
Abedin Abdallah ◽  
Evera Elemba ◽  
Qingzhen Zhong ◽  
Zewei Sun
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Immune System ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Nutrition And Health ◽  
Nitrogenous Compounds ◽  
Dietary Amino Acids ◽  
Host Nutrition ◽  
Chain Fatty Acids

The gastrointestinal tract (GIT) of humans and animals is host to a complex community of different microorganisms whose activities significantly influence host nutrition and health through enhanced metabolic capabilities, protection against pathogens, and regulation of the gastrointestinal development and immune system. New molecular technologies and concepts have revealed distinct interactions between the gut microbiota and dietary amino acids (AAs) especially in relation to AA metabolism and utilization in resident bacteria in the digestive tract, and these interactions may play significant roles in host nutrition and health as well as the efficiency of dietary AA supplementation. After the protein is digested and AAs and peptides are absorbed in the small intestine, significant levels of endogenous and exogenous nitrogenous compounds enter the large intestine through the ileocaecal junction. Once they move in the colonic lumen, these compounds are not markedly absorbed by the large intestinal mucosa, but undergo intense proteolysis by colonic microbiota leading to the release of peptides and AAs and result in the production of numerous bacterial metabolites such as ammonia, amines, short-chain fatty acids (SCFAs), branched-chain fatty acids (BCFAs), hydrogen sulfide, organic acids, and phenols. These metabolites influence various signaling pathways in epithelial cells, regulate the mucosal immune system in the host, and modulate gene expression of bacteria which results in the synthesis of enzymes associated with AA metabolism. This review aims to summarize the current literature relating to how the interactions between dietary amino acids and gut microbiota may promote host nutrition and health.

scholarly journals Genetic biomarkers in the VEGF pathway predicting response to anti-VEGF therapy in age-related macular degeneration

2019 ◽  
Vol 4 (1) ◽  
pp. e000273
Author(s):  
Irina Balikova ◽  
Laurence Postelmans ◽  
Brigitte Pasteels ◽  
Pascale Coquelet ◽  
Janet Catherine ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Treatment Response ◽  
Multiple Testing ◽  
Age Related Macular Degeneration ◽  
Patient Specific ◽  
Multiple Testing Correction ◽  
Anti Vegf ◽  
Age Related ◽  
Vegf Pathway

ObjectiveAge-related macular degeneration (ARMD) is a leading cause of visual impairment. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard treatment for wet ARMD. There is however, variability in patient responses, suggesting patient-specific factors influencing drug efficacy. We tested whether single nucleotide polymorphisms (SNPs) in genes encoding VEGF pathway members contribute to therapy response.Methods and analysisA retrospective cohort of 281 European wet ARMD patients treated with anti-VEGF was genotyped for 138 tagging SNPs in the VEGF pathway. Per patient, we collected best corrected visual acuity at baseline, after three loading injections and at 12 months. We also registered the injection number and changes in retinal morphology after three loading injections (central foveal thickness (CFT), intraretinal cysts and serous neuroepithelium detachment). Changes in CFT after 3 months were our primary outcome measure. Association of SNPs to response was assessed by binomial logistic regression. Replication was attempted by associating visual acuity changes to genotypes in an independent Japanese cohort.ResultsAssociation with treatment response was detected for seven SNPs, including in FLT4 (rs55667289: OR=0.746, 95% CI 0.63 to 0.88, p=0.0005) and KDR (rs7691507: OR=1.056, 95% CI 1.02 to 1.10, p=0.005; and rs2305945: OR=0.963, 95% CI 0.93 to 1.00, p=0.0472). Only association with rs55667289 in FLT4 survived multiple testing correction. This SNP was unavailable for testing in the replication cohort. Of six SNPs tested for replication, one was significant although not after multiple testing correction.ConclusionIdentifying genetic variants that define treatment response can help to develop individualised therapeutic approaches for wet ARMD patients and may point towards new targets in non-responders.

scholarly journals 2dFDR: a new approach to confounder adjustment substantially increases detection power in omics association studies

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sangyoon Yi ◽  
Xianyang Zhang ◽  
Lu Yang ◽  
Jinyan Huang ◽  
Yuanhang Liu ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Statistical Power ◽  
Association Studies ◽  
Control Procedure ◽  
Multiple Testing Correction ◽  
New Approach ◽  
False Discovery ◽  
Traditional Procedure ◽  
Extensive Evaluation ◽  
Confounder Adjustment

AbstractOne challenge facing omics association studies is the loss of statistical power when adjusting for confounders and multiple testing. The traditional statistical procedure involves fitting a confounder-adjusted regression model for each omics feature, followed by multiple testing correction. Here we show that the traditional procedure is not optimal and present a new approach, 2dFDR, a two-dimensional false discovery rate control procedure, for powerful confounder adjustment in multiple testing. Through extensive evaluation, we demonstrate that 2dFDR is more powerful than the traditional procedure, and in the presence of strong confounding and weak signals, the power improvement could be more than 100%.

Sign in / Sign up

Export Citation Format

Share Document