Academic journal article Environmental Health Perspectives

An Exposome Perspective on Environmental Enteric Dysfunction

Academic journal article Environmental Health Perspectives

An Exposome Perspective on Environmental Enteric Dysfunction

Article excerpt

Introduction

Environmental enteropathy (EE) and environmental enteric dysfunction (EED) are terms used to describe the same pathophysiological, subclinical condition of reduced small intestinal barrier and absorptive function that has high prevalence among children living in low- to middle-income countries where poor hygiene, inadequate sanitation, and malnutrition pervade (Crane et al. 2015; Keusch et al. 2013). The spectrum of EED involves structural and functional changes to the gastrointestinal tract (GI) that may include, but not be limited to, altered villous architecture, impaired mucosal immunity, nutrient malabsorption, and growth faltering (Lin et al. 2013; Lindenbaum et al. 1972). Chronic enteric pathogen exposures, including asymptomatic infections, and intestinal permeability in young children have thus far been central to EED research (Salazar-Lindo et al. 2004). However, we suggest that we explore the possible role for diversity of environmental toxicant exposures as well as dysbiosis of the gut microbiome from birth to 2 years of age to address major gaps in our knowledge of EED. The host burden and the host responses to toxicant exposures are highlighted in the concept of an "enteric dysfunction exposome" (Vrijheid et al. 2014). Across global geography and age groups, EED may be influenced in ways that have not yet been connected to existing knowledge of toxicologic importance, and this commentary highlights the compelling case for xenobiotics to be investigated in EED etiology. The enteric dysfunction exposome would not be limited to enteric pathogens and mycotoxins, but would encompass chemical classes for a wide range of environmental toxicants [i.e., endocrine disruptors, trace heavy metals, persistent organic pollutants (POPs), volatile organic chemicals (VOCs), and behaviors] (Miller and Jones 2014). The presence of chemical exposures in maternal blood and breast milk may affect infant immune tolerance, gut microbiome colonization, small intestinal development, and nutrient availability and absorption during in utero, prenatal, and postnatal periods; yet these combination of factors remain poorly characterized in EED-endemic regions (Crane et al. 2015; Gordon et al. 2012; Rappaport et al. 2014; Vrijheid et al. 2014). Thus, EED evaluation should include xenobiotic exposures that can be monitored noninvasively through blood, urine, saliva, and/or stool using both nontargeted omics-based and targeted measurements of exogenous and endogenous small molecules (Keusch et al. 2014). This approach exhibits strong potential to not only identify a suite of reliable EED exposure biomarkers but also design interventions that can perturb an EED-susceptible exposome (Rappaport 2011; Rappaport and Smith 2010; Vrijheid et al. 2014).

Studies in Bangladesh (Lin et al. 2013), Brazil (dos Reis et al. 2007), The Gambia (Campbell et al. 2003, 2004), Nepal (Langford et al. 2011), Malawi (Agapova et al. 2013; Galpin et al. 2005), and Tanzania (Mduma et al. 2014) demonstrate that EED is widespread and pervasive. The current list of EED-associated morbidities provides a strong rationale for identifying biomarkers, diagnostics, preventive agents, and sustainable treatment solutions (Keusch et al. 2014). Along with prevalent severe acute malnutrition--and undernutrition-related childhood mortalities, stunting is postulated to be secondary to EED (Keusch et al. 2013), with EED being a possible contributor to multiple generations of the 171 million children being affected by stunting globally (de Onis et al. 2013). In a case-control study of 202 stunted Zimbabwean infants, a measurement of the biomarkers of intestinal inflammation revealed that exposure to low-grade, chronic inflammation in utero and during early postnatal phases of life was associated with stunting that was likely due to extensive enteropathy that occurs during infancy (Prendergast et al. 2014). We suggest that the milieu of EED causative agents, epigenetic, and genetic factors merit elucidation in order to fill the gap in our knowledge regarding when and how EED can be controlled or prevented. …

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