Duodenal transcriptomics demonstrates signatures of tissue inflammation and immune cell infiltration in children with environmental enteric dysfunction across global centers.

Autor:	Marie C; Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States. Electronic address: csm8r@virginia.edu., Das S; Nutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh., Coomes D; Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, United States., Ahmed T; Nutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh., Ali SA; Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan., Iqbal J; Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan., Kelly P; Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom., Mahfuz M; Nutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh., Moore SR; Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, United States., Petri WA Jr; Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States., Tarr PI; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States., Denson LA; Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Jazyk:	angličtina
Zdroj:	The American journal of clinical nutrition [Am J Clin Nutr] 2024 Sep; Vol. 120 Suppl 1, pp. S51-S64.
DOI:	10.1016/j.ajcnut.2024.02.023
Abstrakt:	Background: Environmental enteric dysfunction (EED) is an inflammatory condition of the small intestine that is prevalent in children residing in low- and middle-income countries. EED is accompanied by profound histopathologic changes in the small bowel, loss of absorptive capacity, increased intestinal permeability, increased microbial translocation, and nutrient loss. Objectives: We sought to identify dysregulated genes and pathways that might underlie pediatric EED. Methods: RNA-sequencing libraries were generated from endoscopically obtained duodenal tissue from undernourished children with EED from 3 prospective cohorts of children with EED. The EED transcriptome was defined in comparison to North American children without EED. Weighted gene coexpression network analysis (WGCNA) was tested for gene modules associated with EED and its histologic features. Results: The 1784 upregulated genes in EED were highly enriched for immune and inflammatory processes, including IL-17 and JAK-STAT signaling, and cytokine-cytokine receptor interactions. The 1388 downregulated genes included genes corresponding to xenobiotic metabolism, detoxification, and antioxidant capacities. A gene coexpression module enriched for antimicrobial responses and chemokine activity was significantly associated with villous blunting, goblet cell depletion, and overall histologic severity of EED. Conclusions: The transcriptome signatures of EED include specific innate and adaptive immune responses that are consistently elevated across study centers, coupled with reduced detoxification and antioxidant capacities. These data may have implications for targeted interventions to improve EED outcomes. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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