Pathogenesis, Clinical and Biological Predictors of Growth in Environmental enteric dysfunction (EED): An Infant Birth Inception Cohort

Environmental enteric dysfunction (EED) is a major impediment to the Sustainable Development Goals of improved childhood survival and healthy growth worldwide. Few studies have directly examined the affected intestine, limiting the development of effective interventions. The Study of Environmental Enteropathy and Malnutrition (SEEM, Pakistan) followed 416 at-risk children prospectively from birth to 24 months of age in a rural district of Pakistan with a high prevalence of undernutrition. The duodenal genome-wide methylome and transcriptome was determined in 52 undernourished SEEM participants refractory to nutritional interventions and 42 North American healthy controls and celiac disease patients. Biomarkers were measured at 9 months and tested for association with growth at 24 months in training (n=166) and validation (n=84) groups within SEEM. DNA methylation was assessed in Duodenal biopsies from undernurished SEEM participants, and north American healthy controls. DNA was extracted, bisulfite converted and genome-wide DNA methylation was interrogated using the HumanMethylationEPIC BeadChip (Illumina).