{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "SUNY Downstate Health Sciences University, Brooklyn, NY",
    "Department of Pediatrics and Child Health, Medical College, The Aga Khan University, Karachi-74800, Pakistan",
    "Duke University Medical Center, Durham, NC",
    "CITRIC Center for Bioinformatics and Computational Biology, Department of Pediatrics and Child Health, Medical College, The Aga Khan University, Karachi-74800, Pakistan",
    "University of Virginia, Charlottesville, VA",
    "Biological and Biomedical Sciences, Aga Khan University, Karachi-74800, Pakistan.",
    "Vanderbilt University Medical Center, Nashville, TN; Department of Community Health Sciences, Medical College"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Shahzaib Khan"
    },
    {
      "affs": [
        2
      ],
      "name": "Nathaniel Ribeiro"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Waqasuddin Khan"
    },
    {
      "affs": [
        4
      ],
      "name": "Nazanin Moradinasab"
    },
    {
      "affs": [
        4
      ],
      "name": "Connor Moore"
    },
    {
      "affs": [
        1
      ],
      "name": "Javairia Khalid"
    },
    {
      "affs": [
        1
      ],
      "name": "M. Farrukh Qazi"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "M. Mohsin Mannan"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Najeeha Talat Iqbal",
      "orcid": "0000-0003-4026-5655"
    },
    {
      "affs": [
        6
      ],
      "name": "Lauren J. Klein",
      "orcid": "0000-0003-1076-8518"
    },
    {
      "affs": [
        2
      ],
      "name": "Adam Greene"
    },
    {
      "affs": [
        5
      ],
      "name": "Asad Ali"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Fyezah Jehan"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "M. Imran Nisar",
      "orcid": "0000-0002-2378-4720"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Sana Syed"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e2ddy6vaywnje.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.25.760166",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.25.760166v1.full",
  "id": "e2ddy6vaywnje",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.25.760166v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "systems biology"
    ],
    [
      "heading",
      "Article"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.25.760166v1.full.pdf",
  "pmcid": "PMC13733850",
  "pmid": "42990336",
  "published": "2026-10-25",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/e2ddy6vaywnje.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:21:20Z",
      "native_id": "10.64898/2026.10.25.760166",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.25.760166v1"
    },
    {
      "first_seen": "2026-11-08T12:23:32Z",
      "native_id": "PMC13733850",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.25.760166"
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  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:systems biology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Amino Acid Metabolic Signature Links Pediatric Environmental Enteric Dysfunction to Maternal-Fetal Growth Restriction Across Two Independent Cohorts",
  "title_text": "Amino Acid Metabolic Signature Links Pediatric Environmental Enteric Dysfunction to Maternal-Fetal Growth Restriction Across Two Independent Cohorts",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:32Z",
  "url": "https://research.draconitic.com/paper/e2ddy6vaywnje",
  "venue": "bioRxiv",
  "versions": []
}