Environmental enteric dysfunction includes a broad spectrum of inflammatory responses and epithelial repair processes.

Environmental enteric dysfunction (EED), a chronic diffuse inflammation of the small intestine, is associated with stunting in children in the developing world. The pathobiology of EED is poorly understood because of the lack of a method to elucidate the host response. This study utilized a novel microarray method to interrogate the host transcriptome in feces in Malawian children with EED. Our data showed that the children studied had a range of %L values, consistent a spectrum of EED from normal to severe. We identified 12 transcripts associated with the severity of EED, including chemokines that stimulate T-cell proliferation, Fc fragments of multiple immunoglobulin families, interferon-induced proteins, activators of neutrophils and B-cells, and mediators that dampen cellular responses to hormones. EED associated transcripts mapped to pathways related to cell adhesion, and responses to a broad spectrum of viral, bacterial and parasitic microbes and enhanced phagocytosis. Several mucins, regulatory factors and protein kinases associated with the maintenance of the mucous layer were expressed less in children with EED than normal children. In conclusion, EED represents the focused activation of elements of the immune system and is associated with widespread intestinal barrier disruption. The differentially expressed transcripts may be explored as potential biomarkers.

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Yu J, Ordiz MI, Stauber J, Shaikh N, Trehan I, Barnell E, Head RD, Maleta K, Tarr PI, Manary MJ