Abstract

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 EE is multifactorial. Overall, exposure contaminated food and water leads to a generalized state of intestinal inflammation. The inflammatory response results in multiple pathological changes to the gastrointestinal tract, including:

- Smaller villi

- Larger crypts (called crypt hyperplasia)

- Increased permeability

- 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 gold-standard diagnostic test is intestinal biopsy. However, this test is invasive and unnecessary for most patients.

Prevention is the strongest and most reliable option for preventing EE and its effects. Therefore, prevention and treatment of EE are often discussed together.

Signs and symptoms

Environmental enteropathy is believed to result in chronic malnutrition and subsequent growth stunting (low height-for-age measurement) as well as other child development deficits.

Signs and symptoms | Short-term

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.

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".

Diagnosis

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

- Dual sugar permeability (lactose-to-mannitol ratio)

- Intestinal inflammation

- Alpha-1 anti-trypsin

- Neopterin

- Myeloperoxidase

- Exocrine (hormonal) markers

- Bacterial translocation markers

- Endotoxin core antibody

- Markers of systemic inflammation

- Alpha-1 glycoprotein

- C-reactive protein (CRP)

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.

Diagnosis | Classification

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.

Prevention and treatment

Prevention focuses on improving sanitation of water and food sources.

Treatment focuses on addressing the central components of intestinal inflammation, bacterial overgrowth and nutritional supplementation.

Research initiatives

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