Amino Acid Metabolic Signature Links Pediatric Environmental Enteric Dysfunction to Maternal-Fetal Growth Restriction Across Two Independent Cohorts
7 affiliations
- 1SUNY Downstate Health Sciences University, Brooklyn, NY
- 2Department of Pediatrics and Child Health, Medical College, The Aga Khan University, Karachi-74800, Pakistan
- 3Duke University Medical Center, Durham, NC
- 4CITRIC Center for Bioinformatics and Computational Biology, Department of Pediatrics and Child Health, Medical College, The Aga Khan University, Karachi-74800, Pakistan
- 5University of Virginia, Charlottesville, VA
- 6Biological and Biomedical Sciences, Aga Khan University, Karachi-74800, Pakistan.
- 7Vanderbilt University Medical Center, Nashville, TN; Department of Community Health Sciences, Medical College
Abstract
Environmental Enteric Dysfunction (EED) is a leading contributor to childhood stunting. Most EED literature derives from postnatal pediatric cohorts, leaving unclear how much of the metabolic signature reflects acquired intestinal pathology versus growth restriction originating earlier. We applied genome-scale metabolic modeling to explore whether metabolic features of pediatric EED overlap with those of maternal plasma proteomes associated with adverse early-life growth. Duodenal transcriptomics from the Study of Environmental Enteropathy and Malnutrition (SEEM; 52 children with EED, 24 controls) and maternal plasma proteomics from the Alliance for Maternal and Newborn Health Improvement (AMANHI; n = 2,485 pregnant women) were integrated with the Human1 model using Reaction Inclusion by Parsimony and Transcript Distribution (RIPTiDe), followed by flux sampling and Linear Discriminant Analysis, across five growth-related proxies (small-for-gestational-age, low birth weight, preterm birth, stunting, and wasting). Amino acid and nucleotide metabolism were prominent among the top discriminating reactions in EED and most proxies. Of the 50 reactions distinguishing EED from control, 24 (48%) were among the top reactions in at least one proxy, and 19 (38%) with low birth weight, the largest of any proxy. These exploratory findings suggest shared metabolic pathways across tissues and life stages and motivate longitudinal studies.
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BibTeX
@misc{khan2026amino,
title = {{Amino Acid Metabolic Signature Links Pediatric Environmental Enteric Dysfunction to Maternal-Fetal Growth Restriction Across Two Independent Cohorts}},
author = {Shahzaib Khan and Nathaniel Ribeiro and Waqasuddin Khan and Nazanin Moradinasab and Connor Moore and Javairia Khalid and M. Farrukh Qazi and M. Mohsin Mannan and Najeeha Talat Iqbal and Lauren J. Klein and Adam Greene and Asad Ali and Fyezah Jehan and M. Imran Nisar and Sana Syed},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.25.760166},
url = {https://www.biorxiv.org/content/10.64898/2026.10.25.760166v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Amino Acid Metabolic Signature Links Pediatric Environmental Enteric Dysfunction to Maternal-Fetal Growth Restriction Across Two Independent Cohorts
AU - Shahzaib Khan
AU - Nathaniel Ribeiro
AU - Waqasuddin Khan
AU - Nazanin Moradinasab
AU - Connor Moore
AU - Javairia Khalid
AU - M. Farrukh Qazi
AU - M. Mohsin Mannan
AU - Najeeha Talat Iqbal
AU - Lauren J. Klein
AU - Adam Greene
AU - Asad Ali
AU - Fyezah Jehan
AU - M. Imran Nisar
AU - Sana Syed
PY - 2026
DA - 2026/10/25
PB - bioRxiv
DO - 10.64898/2026.10.25.760166
UR - https://www.biorxiv.org/content/10.64898/2026.10.25.760166v1
AB - Environmental Enteric Dysfunction (EED) is a leading contributor to childhood stunting. Most EED literature derives from postnatal pediatric cohorts, leaving unclear how much of the metabolic signature reflects acquired intestinal pathology versus growth restriction originating earlier. We applied genome-scale metabolic modeling to explore whether metabolic features of pediatric EED overlap with those of maternal plasma proteomes associated with adverse early-life growth. Duodenal transcriptomics from the Study of Environmental Enteropathy and Malnutrition (SEEM; 52 children with EED, 24 controls) and maternal plasma proteomics from the Alliance for Maternal and Newborn Health Improvement (AMANHI; n = 2,485 pregnant women) were integrated with the Human1 model using Reaction Inclusion by Parsimony and Transcript Distribution (RIPTiDe), followed by flux sampling and Linear Discriminant Analysis, across five growth-related proxies (small-for-gestational-age, low birth weight, preterm birth, stunting, and wasting). Amino acid and nucleotide metabolism were prominent among the top discriminating reactions in EED and most proxies. Of the 50 reactions distinguishing EED from control, 24 (48%) were among the top reactions in at least one proxy, and 19 (38%) with low birth weight, the largest of any proxy. These exploratory findings suggest shared metabolic pathways across tissues and life stages and motivate longitudinal studies.
SN - 2692-8205
ER -