Enteropathies in the developing world: neglected effects on global health

Abstract

A spectrum of enteropathies, characterized by small intestinal inflammation, reduced absorptive capacity, and increased intestinal permeability, commonly affect people in developing countries. This subclinical intestinal pathology facilitates microbial translocation across the compromised intestinal barrier, leading to chronic systemic inflammation that may adversely impact health. Environmental enteropathy (EE), ubiquitous among people living in unhygienic conditions, likely mediates two interlinked public health problems of childhood, stunting and anemia, and underlies poor oral vaccine efficacy in developing countries. Human immunodeficiency virus (HIV) enteropathy, which frequently overlaps with EE, may contribute to immune activation and modulate HIV disease progression. The interacting effects of infection and enteropathy drive a vicious cycle that can propagate severe acute malnutrition, which underlies almost half of under-5-y deaths. Enteropathies are therefore highly prevalent, interacting causes of morbidity and mortality in developing countries. Interventions to prevent or ameliorate enteropathies have potential to improve the health of millions of people in developing countries.

Figure 1.

Endoscopic appearance of environmental enteropathy. Endoscopic view of second part of the duodenum showing villi with characteristic changes of environmental enteropathy: fusion of villi so that instead of a finger-like appearance they take on a leaf-shaped appearance. Sometimes villous fusion goes further and takes on a cerebriform (sulcus and gyrus) appearance. Endoscopic image from Endoscopy Unit, University Teaching Hospital, Lusaka (P. Kelly).

Figure 2.

Proposed causal pathway linking enteropathy with adverse health outcomes in developing countries. Several biologic, environmental, and possibly genetic factors promote the development of enteropathy, which is characterized by abnormal intestinal architecture and increased permeability. Enteropathy enables microbial translocation, which causes generalized activation of the innate and adaptive immune system. This chronic inflammatory pathway may mediate stunting and anemia in children living in developing countries; exacerbate immune activation and CD4 decline in human immunodeficiency virus (HIV)-infected individuals; and reduce oral vaccine efficacy.

Figure 3.

Overlapping causes of enteropathy in the developing world. There are multiple underlying causes of enteropathy among people living in developing countries, which overlap on a background of environmental enteropathy. Environmental enteropathy is almost universal among people living in conditions of poverty. Overlapping causes of enteropathy shown here are based on known associations, but the size of each overlap is speculative and is not meant to represent prevalence. MN = micronutrient; SAM = severe acute malnutrition.