Interactions between intestinal pathogens, enteropathy and malnutrition in developing countries

Abstract

Purpose of review: This review focuses on recent data highlighting the interactions between intestinal pathogens, enteropathy and malnutrition in developing countries, which drive morbidity and mortality and hinder the long-term developmental potential of children.

Recent findings: Diarrhoea remains the second commonest cause of death in children below 5 years, and malnutrition underlies 45% of all child deaths. Even in the absence of diarrhoea, subclinical pathogen carriage and enteropathy are almost universal in developing countries. Here, we review recent studies addressing the causes and consequences of diarrhoea; emerging data on environmental influences that govern postnatal development of the gut and microbiota; current concepts of environmental enteric dysfunction; and recent intervention trials in the field. We highlight the interactions between these processes, whereby intestinal pathogens drive a cycle of gut damage, malabsorption, chronic inflammation and failed mucosal regeneration, leading to malnutrition and susceptibility to further enteric infections.

Summary: Efforts to improve child survival and long-term developmental potential need to address the overlapping and interacting effects of diarrhoea, enteropathy and malnutrition. Recent insights from human and animal studies suggest potential targets for intervention.

Box 1

no caption available

FIGURE 1

Interactions between intestinal pathogens, enteropathy and malnutrition. Contamination of the environment leads to increased exposure to intestinal pathogens that damage the mucosa and, because of failure to repair the damage, lead to microbial translocation, inflammation/sepsis and malabsorption. Several of these components reinforce mucosal damage in a positive feedback loop, exacerbating the cycle of malnutrition and infection as originally observed by Scrimshaw et al. in the 1960 s. Potential points for intervention include (1) water and sanitation (WASH) interventions to prevent enteropathogen exposure; (2) antimicrobial, probiotic or prebiotic agents to reduce gut colonization/dysbiosis; (3) factors (still unidentified) to enhance mucosal healing; (4) specific micronutrient supplementation to overcome specific absorptive defects, such as zinc to promote Paneth cell function; (5) anti-infective agents to reduce microbial translocation and prevent sepsis; and (6) anti-inflammatory interventions. This list is far from exhaustive.