Environmental enteric dysfunction: gut and microbiota adaptation in pregnancy and infancy

Environmental enteric dysfunction (EED) is a subclinical syndrome of intestinal inflammation, malabsorption and barrier disruption that is highly prevalent in low- and middle-income countries in which poverty, food insecurity and frequent exposure to enteric pathogens impair growth, immunity and neurodevelopment in children. In this Review, we discuss advances in our understanding of EED, intestinal adaptation and the gut microbiome over the ‘first 1,000 days’ of life, spanning pregnancy and early childhood. Data on maternal EED are emerging, and they mirror earlier findings of increased risks for preterm birth and fetal growth restriction in mothers with either active inflammatory bowel disease or coeliac disease. The intense metabolic demands of pregnancy and lactation drive gut adaptation, including dramatic changes in the composition, function and mother-to-child transmission of the gut microbiota. We urgently need to elucidate the mechanisms by which EED undermines these critical processes so that we can improve global strategies to prevent and reverse intergenerational cycles of undernutrition.