Implications of Acquired Environmental Enteric Dysfunction for Growth and Stunting in Infants and Children Living in Low- and Middle-Income Countries

Abstract

Changes in small bowel function early in infancy in developing countries are increasingly being demonstrated, probably accompanied by altered mucosal architecture in most individuals, including reduced enterocyte mass and evidence of immune activation and inflammation in the mucosa. These alterations appear to be the result of factors of uncertain nature in the environment, and may be a cause of growth faltering and stunting in young children. For these reasons, this constellation of findings is being referred to as environmental enteropathy, or as we propose herein, environmental enteric dysfunction. If the causes were known and effective interventions were available, strategies and policies to intervene at—or possibly before—birth could be developed and promoted in order to prevent subsequent malnutrition and recurrent infection, which are known to interact in a cyclical and synergistic manner in a downward clinical course often ending in death. Resources would be mobilized and applied differently, and the emphasis would change from treatment to prevention. In order to move in this highly desired direction, investments in research will be required to establish the criteria to assess environmental enteric dysfunction, determine its predictive value for growth faltering and stunting, identify the causes, and propose and test potential interventions. The concepts and tools are available. What is required is the decision to move forward along this pathway to better health for infants and children in low-income countries.

Malnutrition and vaccination in developing countries

“…It has also been noted since the 1960s that a small intestinal abnormality, originally termed tropical enteropathy, is almost universally seen among apparently healthy people living in developing countries [18,19], but it is only relatively recently that attention has refocused on this condition. A series of studies from the Gambia [20,21] showed a relationship between enteropathy and impaired linear growth in infants, and recent studies [22][23][24] have further highlighted the role that this gut pathology, now renamed environmental enteric dysfunction (EED) [25], may have in stunting malnutrition. The impact of enteropathy on mucosal immune function remains unclear, because of the difficulties in obtaining gut biopsies from young children, but EED may be one of the factors underlying the poor performance of oral vaccines in developing countries, as discussed in another paper in this issue [26].…”

Probiotics, antibiotics and the immune responses to vaccines

“…This is reflected initially in an increase in the release of pro-inflammatory cytokines and by inflammatory cell infiltration of the gut, which is followed by enteric T-cell stimulation and a cell-mediated enteropathy [42,43]. This pathology is believed to lead to an increase in intestinal permeability and malabsorption resulting in linear growth faltering and chronic malnutrition, and may also affect the immune response [40,44].…”

“…These data also suggest the possibility that combinations of known and unknown bacteria, viruses and parasites may contribute to the dysregulated gut inflammation seen in environmental enteropathy. Environmental enteropathy or tropical enteropathy or environmental enteric dysfunction is a sub-clinical condition characterized by histological and functional abnormalities in the small intestine and which appears common in children living in resource-poor settings [40]. The condition is thought to reflect constant exposure to faecal pathogens in the environment, resulting in chronic intestinal inflammation [41].…”

Neurodevelopment, Nutrition, and Inflammation: The Evolving Global Child Health Landscape

“…58 EE with disrupted intestinal barrier function, intestinal inflammation, and impaired absorptive function is postulated to impair early childhood growth and neurodevelopment. The fact that inflammation during key life periods may play a critical role in affecting nutrition, EE, and development has been well recognized for well over 2 decades 59 and was convincingly demonstrated in a series of studies in Malawi and Zimbabwe.…”