|Histological evidence of enteropathy (inflammatory infiltrate, villus blunting) seen in this intestinal biopsy from a child with malnutrition.|
|Symptoms||Asymptomatic (most common), altered stool consistency, increased stool frequency, weight loss|
|Complications||Malnutrition, malabsorption, growth stunting, developmental delay, impaired response to oral vaccines|
|Causes||Unsanitary food and water sources, fecal-oral contamination, chronic enteric infections, mucosal inflammation|
|Diagnostic method||Intestinal biopsy (gold standard), abnormal sugar absorption test, clinical (significantly more common)|
|Differential diagnosis||Tropical sprue|
Environmental enteropathy (EE) (also known as tropical enteropathy or environmental enteric dysfunction) is a disorder of chronic intestinal inflammation. EE is most common amongst children living in low-resource settings. Acute symptoms are typically minimal or absent. EE can lead to malnutrition, anemia (iron-deficiency anemia and anemia of chronic inflammation), growth stunting, impaired brain development, and impaired response to oral vaccinations.
The cause of EE is multifactorial. Overall, exposure to contaminated food and water leads to a generalized state of intestinal inflammation. The inflammatory response results in multiple pathological changes to the gastrointestinal tract: Smaller villi, larger crypts (called crypt hyperplasia), increased permeability, and inflammatory cell build-up within the intestines. These changes result in poor absorption of food, vitamins and minerals.
Standardized, clinically practical diagnostic criteria do not exist. The most accurate diagnostic test is intestinal biopsy. However, this test is invasive and unnecessary for most patients.
Signs and symptoms
EE is rarely symptomatic and is considered a subclinical condition. However, adults may have mild symptoms or malabsorption such as altered stool consistency, increased stool frequency and weight loss.
- Malnutrition 
- Growth and physical development 
- The first two years (and the prior 9 months of fetal life) are critical for linear growth. Stunting is an easy to measure symptom of these child development deficits.
- Neurocognitive (brain development) 
- Effect on oral vaccination 
- Many oral vaccines, both live and non-living, have proven to be less immunogenic or less protective when administered to infants, children or adults living in low socioeconomic conditions in developing countries than they are when used in industrialized countries. Widespread EE is hypothesized to be a contributing cause for this observation.
Causes and mechanism
The development of EE is multifactorial, but predominantly associated with chronic exposure to contaminated food and water. This is especially true in environments where widespread open defecation and lack of sanitation are common.
Long-term exposure to environmental pathogens leads to a generalized state of intestinal inflammation. Chronic inflammation leads to both functional and structural changes which alter gut permeability and ability of the intestine to absorb nutrients.
Specifically, structural changes within the intestine include smaller villi, larger crypts (called crypt hyperplasia), increased permeability, and inflammatory cell build-up within the intestines. These changes result in poor absorption of food, vitamins and minerals – or "modest malabsorption".
The current gold standard diagnostic test for EE is intestinal biopsy and histological analysis. Histological changes observed include:
- Villous blunting
- Crypt hypertrophy
- Villous fusion
- Mucosal inflammation
However, this procedure is considered too invasive, complex and expensive to be implemented as standard of care. As a result, there are various research efforts underway to identify biomarkers associated with EE, which could serve as less invasive, yet representative, tools to screen for and identify EE from stool samples.
In an effort to identify simple, accurate diagnostic tests for EE, the Bill and Melinda Gates Foundation (BMGF) has established an EE biomarkers consortium as part of their Global Grand Challenges initiative (specifically, the Discover Biomarkers of Gut Function challenge).
So far, various biomarkers have been selected and studied based on the current understanding of EE pathophysiology:
- Gut permeability/barrier function
- Intestinal inflammation
- Exocrine (hormonal) markers
- Bacterial translocation markers
- Endotoxin core antibody
- Markers of systemic inflammation
It is postulated that the limited of understanding of EE is partially due to the paucity of reliable biomarkers, making it difficult for researchers to track the epidemiology of the condition and assess the efficacy of interventions.
In the 1960s, researchers reported a syndrome of non-specific histopathological and functional changes to the small intestine in individuals living in unsanitary conditions. This syndrome was observed predominantly in tropical regions across Latin America, sub-Saharan Africa and Asia. The geographic distribution of the syndrome lead to the original term of "tropical enteropathy" (sometimes also "tropical jejunopathy").
Following initial reports, further investigation revealed that these symptoms were not specific to tropical climates. For example, individuals in more wealthy tropical countries, such as Qatar and Singapore, did not exhibit these symptoms. Similarly, subsequent studies have shown this condition to be common across the developing world, closely associated with impoverished conditions but independent of climate or geography. As a result, the term "environmental enteropathy" was introduced to specify that this condition is not only found in tropical areas and is believed to be caused by environmental factors.
Treatment focuses on addressing the central components of intestinal inflammation, bacterial overgrowth and nutritional supplementation.
Another important factor might be contaminated soil in child play spaces, often caused by the presence of livestock such as chicken in the household. Creating a clean play space might therefore be an effective preventive measure for EE in toddlers.
There are multiple large-field, multi-country research initiatives focusing on strategies to prevent and treat EE.
- The MAL-ED project
- The Alive and Thrive nutrition project
- The Sanitation, Hygiene and Infant Nutrition Efficacy (SHINE) Trial (ClinicalTrials.gov identifier: NCT01824940)
- The WASH Benefits Study
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