ArticleGastroenterology2021
Mucosal Genomics Implicate Lymphocyte Activation and Lipid Metabolism in Refractory Environmental Enteric Dysfunction.
Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03588013 (Study of Environmental Enteropathy and Malnutrition in Pakistan), which is not on this map. Cited by 42 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Study of Environmental Enteropathy and Malnutrition in Pakistan
Who cites it
42 citing papers in PubMed, 77 citations in OpenAlex.
- Bile Acid Profiling Reveals Distinct Signatures in Undernourished Children with Environmental Enteric Dysfunction.The Journal of nutrition · 2021Trial
- Tight Junction Defects in Aganglionic and Ganglionic Colon in Children With Hirschsprung Disease.Laboratory investigation; a journal of technical methods and pathology · 2026Article
- Disrupting the vicious cycle of malnutrition and enteropathy: advancing strategies to improve child physical and neurocognitive outcomes.Frontiers in public health · 2026Review
- Plasma lipopolysaccharide levels predict mortality in acutely ill children in Low- and Middle-Income Countries.Nature communications · 2025Article
- Article
- Fermented pickles improve gut microbiota and immune profile in women in a community trial in rural Pakistan.Scientific reports · 2025Article
- Integrated fecal macrogenomic and metabolomic analyses reveal celiac disease flora and metabolic profiles associated with Chinese populations.Journal of translational medicine · 2025Article
- Exact model-free function inference using uniform marginal counts for null population.Bioinformatics (Oxford, England) · 2025Article
- Faecal biomarkers in children with coeliac disease: A way forward?Acta paediatrica (Oslo, Norway : 1992) · 2025Article
- Duodenal transcriptomics demonstrates signatures of tissue inflammation and immune cell infiltration in children with environmental enteric dysfunction across global centers.The American journal of clinical nutrition · 2024Article
- Histopathology underlying environmental enteric dysfunction in a cohort study of undernourished children in Bangladesh, Pakistan, and Zambia compared with United States children.The American journal of clinical nutrition · 2024Article
- Enteric pathogens relationship with small bowel histologic features of environmental enteric dysfunction in a multicountry cohort study.The American journal of clinical nutrition · 2024Article
- Multiplexed immunohistochemical evaluation of small bowel inflammatory and epithelial parameters in environmental enteric dysfunction.The American journal of clinical nutrition · 2024Article
- The Environmental Enteric Dysfunction Biopsy Initiative (EEDBI) Consortium: mucosal investigations of environmental enteric dysfunction.The American journal of clinical nutrition · 2024Article
- Article
- Article
- Diet-omics in the Study of Urban and Rural Crohn disease Evolution (SOURCE) cohort.Nature communications · 2024Article
- Colonization during a key developmental window reveals microbiota-dependent shifts in growth and immunity during undernutrition.Microbiome · 2024Article
- Small Intestine Bacterial Overgrowth is associated with increased Campylobacter and epithelial injury in duodenal biopsies of Bangladeshi children.PLoS neglected tropical diseases · 2024Article
- Current Understanding ofCurrent tropical medicine reports · 2024Article
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsEnvironmental enteric dysfunction (EED) limits the Sustainable Development Goals of improved childhood growth and survival. We applied mucosal genomics to advance our understanding of EED.
methodsThe Study of Environmental Enteropathy and Malnutrition (SEEM) followed 416 children from birth to 24 months in a rural district in Pakistan. Biomarkers were measured at 9 months and tested for association with growth at 24 months. The duodenal methylome and transcriptome were determined in 52 undernourished SEEM participants and 42 North American controls and patients with celiac disease.
resultsAfter accounting for growth at study entry, circulating insulin-like growth factor-1 (IGF-1) and ferritin predicted linear growth, whereas leptin correlated with future weight gain. The EED transcriptome exhibited suppression of antioxidant, detoxification, and lipid metabolism genes, and induction of anti-microbial response, interferon, and lymphocyte activation genes. Relative to celiac disease, suppression of antioxidant and detoxification genes and induction of antimicrobial response genes were EED-specific. At the epigenetic level, EED showed hyper-methylation of epithelial metabolism and barrier function genes, and hypo-methylation of immune response and cell proliferation genes. Duodenal coexpression modules showed association between lymphocyte proliferation and epithelial metabolic genes and histologic severity, fecal energy loss, and wasting (weight-for-length/height Z < -2.0). Leptin was associated with expression of epithelial carbohydrate metabolism and stem cell renewal genes. Immune response genes were attenuated by giardia colonization.
conclusionsChildren with reduced circulating IGF-1 are more likely to experience stunting. Leptin and a gene signature for lymphocyte activation and dysregulated lipid metabolism are implicated in wasting, suggesting new approaches for EED refractory to nutritional intervention. ClinicalTrials.gov, Number: NCT03588013. (https://clinicaltrials.gov/ct2/show/NCT03588013).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.