Interactions between zinc deficiency and environmental enteropathy in developing countries

Abstract

Zinc deficiency affects one-fifth of the world's population and leads to substantial morbidity and mortality. Environmental enteropathy (EE), a subclinical pathology of altered intestinal morphology and function, is almost universal among people living in developing countries and affects long-term growth and health. This review explores the overlapping nature of these 2 conditions and presents evidence for their interaction. EE leads to impaired zinc homeostasis, predominantly due to reduced absorptive capacity arising from disturbed intestinal architecture, and zinc deficiency exacerbates several of the proposed pathways that underlie EE, including intestinal permeability, enteric infection, and chronic inflammation. Ongoing zinc deficiency likely perpetuates the adverse outcomes of EE by worsening malabsorption, reducing intestinal mucosal immune responses, and exacerbating systemic inflammation. Although the etiology of EE is predominantly environmental, zinc deficiency may also have a role in its pathogenesis. Given the impact of both EE and zinc deficiency on morbidity and mortality in developing countries, better understanding the relation between these 2 conditions may be critical for developing combined interventions to improve child health.

FIGURE 1

Hypothesized (or plausible) interactions between zinc deficiency and EE. A conceptual framework showing possible interactions between zinc deficiency and intestinal pathology, including pathways through which EE is thought to occur (solid arrows), pathways through which EE may contribute to zinc deficiency (solid bold arrows), and pathways through which zinc deficiency may contribute to or exacerbate EE (dashed arrows). EE, environmental enteropathy; GI, gastrointestinal.