Intestinal Biopsies for the Evaluation of Environmental Enteropathy and Environmental Enteric Dysfunction

Environmental enteric dysfunction (EED) is a syndrome characterized by impairments of digestion and absorption and intestinal barrier failure in people living in insanitary or tropical environments. There is substantial evidence that it contributes to impaired linear growth of millions of children in low- and middle-income countries, to slowed neurocognitive development, and to diminished responses to oral vaccines. It represents the functional consequences of environmental enteropathy, an asymptomatic inflammatory disorder of the mucosa, and there is considerable overlap with the enteropathy observed in severe clinical malnutrition. The majority of studies of EED have employed functional tests based on lactulose permeation to define the presence of abnormal leak in the gut. However, where intestinal biopsies can safely be collected the opportunity then arises to study the underlying enteropathy in cellular and molecular detail, as well as to measure important functional elements such as enzyme expression. The purpose of this narrative review is to summarize the current understanding of environmental enteropathy obtained from small intestinal biopsies, and prospects for future work. We review histology, electron microscopy, transcription and protein expression, physiological measures, and the microbiome. We conclude that while noninvasive biomarkers of enteropathy and intestinal dysfunction permit large-scale studies of unquestionable value, intestinal biopsies are still required to investigate pathophysiology in depth.