Environmental enteropathy | |
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Other names | Tropical enteropathy or Environmental enteric dysfunction |
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Histological evidence of enteropathy (inflammatory infiltrate, villus blunting) seen in this intestinal biopsy from a child with malnutrition. [1] | |
Specialty | Gastroenterology |
Symptoms | Asymptomatic (most common), altered stool consistency, increased stool frequency, weight loss |
Complications | Malnutrition, malabsorption, growth stunting, developmental delay, impaired response to oral vaccines |
Duration | Chronic |
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 |
Prevention | Sanitation |
Environmental enteropathy (EE or tropical enteropathy or environmental enteric dysfunction or EED) is an acquired small intestinal disorder characterized by gut inflammation, reduced absorptive surface area in small intestine, and disruption of intestinal barrier function. [2] [3] [1] [4] [5] EE is most common amongst children living in low-resource settings. [2] [3] [1] Acute symptoms are typically minimal or absent. [3] EE can lead to malnutrition, anemia (iron-deficiency anemia and anemia of chronic inflammation), [2] stunted growth, impaired brain development, [6] [7] [8] and impaired response to oral vaccinations. [9] [10]
The cause of EE is multifactorial. Overall, exposure to contaminated food and water leads to a generalized state of intestinal inflammation. [2] [3] [1] 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. [3] [1] [11] 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. [2]
Prevention is the strongest and most reliable option for preventing EE and its effects. Therefore, prevention and treatment of EE are often discussed together. [11] [12] [13]
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. [5]
The relationship between dietary intake and infection is difficult to study since it is reciprocal in nature. [15] [16] Further, the gut tissue consumes the nutrients it requires before passage of excess nutrients to the rest of the body. [17] [18] The benefits achieved by improved nutrient intake on environmental enteropathy may thus be independent of nutritional status. Nutrient intake during inflammation is usually decreased.[ citation needed ]
Reports of "poor appetite" by caregivers in LMICs, [19] and restriction of complementary foods during illness [20] is common. Appetite may be reduced both by pro-inflammatory cytokines and leptin [21] and low zinc status, [22] and may be continuous in children with environmental enteropathy. [23] Nutrient availability for growth in environmental enteropathy is further limited due to reduced intestinal surface area and loss of enzymatic activity causing malabsorption of nutrients [24] [25] and, following microbial translocation, retention of circulating nutrients (i.e vitamin A, zinc and iron) in body tissues in order to starve pathogens. [23] Associations between nutrient intake and biomarkers for nutrient status [26] and nutrient status and growth [27] are thus likely distorted in children with inflammation.
The systemic inflammation resulting from microbial translocation will increase basal metabolic rate and nutrient needs by the immune system. [28] At the same time, nutrient losses increase due to intestinal secretion. [29] The associations are thus complex, and further complicated by intestinal host-pathogen-microbiome interactions [30] and the effects of these interactions on intestinal nutrient availability, [31] [32] where additional research is needed. Finally, evidence of whether nutrition interventions may be successful in children with repeated episodes of infection or persistent subclinical infection is scant. [23] Meanwhile, there seems to be agreement that successful interventions to improve complementary feeding practices [33] and reduce stunting [34] [35] must encompass both immediate and underlying causes.
The development of environmental enteropathy (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. [2] [3] [1]
The main cause of environmental enteropathy is likely repeated exposure to enteric pathogens through fecal contamination. [36] [35] [37] Rotavirus, norovirus, cryptosporidum, shigella, campylobacter and E-coli are among the most prevalent causative agents. [38] [39]
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. [2] [3] [1]
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". [2] [3] [1]
The current gold standard diagnostic test for EE is intestinal biopsy and histological analysis. Histological changes observed include: [1]
The key histological features are villous flattening, crypt hyperplasia and inflammation in the epithelium and lamina propria. [34] [40]
However, this procedure is considered too invasive, complex and expensive to be implemented as standard of care. [2] 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. [2] 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). [2]
So far, various biomarkers have been selected and studied based on the current understanding of EE pathophysiology: [2]
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. [11] EE is described as a reversible [41] [42] condition which is probabilistically associated with poor development, but is neither a necessary nor a sufficient cause and may lead to no observable clinical outcomes. [43] This contributes to difficulties encountered when assessing EE.
In the 1960s, researchers reported a syndrome of non-specific histopathological and functional changes to the small intestine in individuals living in unsanitary conditions. [3] 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"). [3]
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. [1] 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. [1] [11] 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. [3]
Prevention focuses on improving access to improved water, sanitation and hygiene (WASH). [13] [6] Another important factor responsible for EE is 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. [44] Some potential strategies to prevent EE are:[ citation needed ]
There is no effective and accepted treatment for EE. Treatment focuses on addressing the central components of intestinal inflammation, bacterial overgrowth and nutritional supplementation. [2] Some potential interventions to improve symptoms associated with EE are:
The role of nutrition in environmental enteropathy is increasingly being recognized. [43] Environmental enteropathy is likely associated with energy deficiency and underweight. Mice fed a moderately energy- and protein deficient diet who are exposed to intestinal pathogens show traits similar to environmental enteropathy. [48] Further, weight gain in malnourished children is shown to improve environmental enteropathy. [49] Severe malnourishment is also likely associated with microbiota immaturity, [50] which might increase environmental enteropathy. [51] The intestinal mucosa turnover is dynamic, nutrient-dependent and rapid, [52] and malnourished children have rate-limiting stores for repairing mucosal damage. [24]
The nutrients known to contribute to intestinal regeneration and improved barrier function are sulphur containing amino acids, [53] glutamine, vitamin A and zinc. [35] [52] Meanwhile, studies investigating associations between glutamine [54] or vitamin A supplementation, [55] [17] serum retinol [56] [57] or zinc supplementation either alone, [58] in combination with vitamin A [59] or with micronutrients and antibiotics [60] and environmental enteropathy show mixed results.
Gut barrier repair and gut function may also be improved by a reduction in the inflammatory response. Short-chain fatty acids (SCFA) result from fermentation of non starch polysaccharides in the colon. [52] It is likely that short-chain fatty acids in addition to zinc [52] and polyunsaturated fatty acids (PUFAs) [61] may reduce gastrointestinal inflammation. Although neither fibre nor polyunsaturated fatty acids provided as supplements improved lactulose:mannitol (L:M) ratio or inflammation in intervention trials, [62] [63] an increased protein and fibre intake from legumes as complementary food, might improve environmental enteropathy. [64] [65] Cessation of breastfeeding and introduction of complementary foods, especially foods with high fibre and protein content, also likely increases microbiota diversity, [66] which might benefit the intestine. As for micronutrient intake and environmental enteropathy, studies from Africa have demonstrated that multiple micronutrient supplementation may improve lactulose:mannitol (L:M) ratio in adults, [67] and transiently in children. [68] Finally, despite the diverse roles attributed to zinc in environmental enteropathy the effect of supplementation as prophylaxis is uncertain. [69] This may partly be due to the perturbed nutrient metabolism occurring in environmental enteropathy.[ citation needed ]
Environmental enteropathy (EE) primarily affects children living in low- and middle-income countries (LMICs). [70] Children living in these countries were found to have enteric pathogens related to EE in their systems throughout much of their early childhoods. [70] Gastrointestinal abnormalities associated with EE are not congenital but are acquired during infancy and persist into adulthood. [71] [72] Such abnormalities tend to develop after the first semester of life and are not present in newborns. [71]
Historically, environmental enteropathy has been prevalent in LMICs. [72] The geographic distribution of environmental enteropathy has shown an increase in incidence in such areas of poor sanitation and hygiene. [70] EE was first described in studies from the 1960-70s conducted in Asia, Africa, the Indian subcontinent, and Central America, during which it was discovered that signs of EE were high among otherwise healthy adults and children. [73] A study from 1971 following US Peace Corps volunteers is often cited as being the first study to demonstrate the ability to acquire and recover from EE according to the environment. [72] Participants experienced symptoms of chronic enteric infection during and shortly after returning from their placement in low- and middle-income countries. [70] Symptoms experienced by those abroad were resolved within one to two years after returning home to the US. [72] These results lead to the suggestion of the environment being a cause of EE, and a later study in Zambia was able to draw similar conclusions. [72] By the early 1990s, environmental enteropathy was found to be a widespread problem affecting infants and children. [72] Today, enteric infections and diarrheal diseases like environmental enteropathy account for 760,000 deaths per year worldwide, making EE the second leading cause of death in children under five years old. [73]
The exact causes and consequences of EE have been difficult to establish due, in part, to the lack of a clear disease definition. [70] However, risk factors do exist and they can be both environmental and nutritional. [70] Preexisting conditions such as micronutrient deficiencies, diarrheal diseases, and various chronic infections all serve as risk factors for EE. [70] Environmental conditions such as poor sanitation and unimproved water sources also contribute to the prevalence of EE. [70] Exposure to environmental microbial agents such as these is thought to be the most important factor in the development of EE. [71]
There are multiple large-field, multi-country research initiatives focusing on strategies to prevent and treat EE. [11]
Kwashiorkor is a form of severe protein malnutrition characterized by edema and an enlarged liver with fatty infiltrates. It is thought to be caused by sufficient calorie intake, but with insufficient protein consumption, which distinguishes it from marasmus. Recent studies have found that a lack of antioxidant micronutrients such as β-carotene, lycopene, other carotenoids, and vitamin C as well as the presence of aflatoxins may play a role in the development of the disease. However, the exact cause of kwashiorkor is still unknown. Inadequate food supply is correlated with occurrences of kwashiorkor; occurrences in high income countries are rare. It occurs amongst weaning children to ages of about five years old.
Diarrhea, also spelled diarrhoea or diarrhœa, is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin with loss of the normal stretchiness of the skin and irritable behaviour. This can progress to decreased urination, loss of skin color, a fast heart rate, and a decrease in responsiveness as it becomes more severe. Loose but non-watery stools in babies who are exclusively breastfed, however, are normal.
Parenteral nutrition (PN) is the feeding of nutritional products to a person intravenously, bypassing the usual process of eating and digestion. The products are made by pharmaceutical compounding entities or standard pharmaceutical companies. The person receives a nutritional mix according to a formula including glucose, salts, amino acids, lipids and vitamins and dietary minerals. It is called total parenteral nutrition (TPN) or total nutrient admixture (TNA) when no significant nutrition is obtained by other routes, and partial parenteral nutrition (PPN) when nutrition is also partially enteric. It is called peripheral parenteral nutrition (PPN) when administered through vein access in a limb rather than through a central vein as central venous nutrition (CVN).
Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety of anaemias.
Micronutrients are essential dietary elements required by organisms in varying quantities to regulate physiological functions of cells and organs. Micronutrients support the health of organisms throughout life.
Tropical sprue is a malabsorption disease commonly found in tropical regions, marked with abnormal flattening of the villi and inflammation of the lining of the small intestine. It differs significantly from coeliac sprue. It appears to be a more severe form of environmental enteropathy.
Short bowel syndrome is a rare malabsorption disorder caused by a lack of functional small intestine. The primary symptom is diarrhea, which can result in dehydration, malnutrition, and weight loss. Other symptoms may include bloating, heartburn, feeling tired, lactose intolerance, and foul-smelling stool. Complications can include anemia and kidney stones.
Enteropathy refers to any pathology of the intestine. Although enteritis specifically refers to an inflammation of the intestine, and is thus a more specific term than "enteropathy", the two terms are sometimes used interchangeably.
Stunted growth, also known as stunting or linear growth failure, is defined as impaired growth and development manifested by low height-for-age. It is a primary manifestation of malnutrition and recurrent infections, such as diarrhea and helminthiasis, in early childhood and even before birth, due to malnutrition during fetal development brought on by a malnourished mother. The definition of stunting according to the World Health Organization (WHO) is for the "height-for-age" value to be less than two standard deviations of the median of WHO Child Growth Standards. Stunted growth is usually associated with poverty, unsanitary environmental conditions, maternal undernutrition, frequent illness, and/or inappropriate feeding practice and care during early years of life.
Vitamin A deficiency (VAD) or hypovitaminosis A is a lack of vitamin A in blood and tissues. It is common in poorer countries, especially among children and women of reproductive age, but is rarely seen in more developed countries. Nyctalopia is one of the first signs of VAD, as the vitamin has a major role in phototransduction; but it is also the first symptom that is reversed when vitamin A is consumed again. Xerophthalmia, keratomalacia, and complete blindness can follow if the deficiency is more severe.
Radiation enteropathy is a syndrome that may develop following abdominal or pelvic radiation therapy for cancer. Many affected people are cancer survivors who had treatment for cervical cancer or prostate cancer; it has also been termed pelvic radiation disease with radiation proctitis being one of the principal features.
Zinc deficiency is defined either as insufficient zinc to meet the needs of the body, or as a serum zinc level below the normal range. However, since a decrease in the serum concentration is only detectable after long-term or severe depletion, serum zinc is not a reliable biomarker for zinc status. Common symptoms include increased rates of diarrhea. Zinc deficiency affects the skin and gastrointestinal tract; brain and central nervous system, immune, skeletal, and reproductive systems.
Animal source foods (ASF) include many food items that come from an animal source such as fish, meat, dairy, eggs and honey. Many individuals consume little ASF or even none for long periods of time by either personal choice or necessity, as ASF may not be accessible or available to these people.
Micronutrient deficiency is defined as the sustained insufficient supply of vitamins and minerals needed for growth and development, as well as to maintain optimal health. Since some of these compounds are considered essentials, micronutrient deficiencies are often the result of an inadequate intake. However, it can also be associated to poor intestinal absorption, presence of certain chronic illnesses and elevated requirements.
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People living with HIV/AIDS face increased challenges in maintaining proper nutrition. Despite developments in medical treatment, nutrition remains a key component in managing this condition. The challenges that those living with HIV/AIDS face can be the result of the viral infection itself or from the effects of anti-HIV therapy (HAART).
Undernutrition in children, occurs when children do not consume enough calories, protein, or micronutrients to maintain good health. It is common globally and may result in both short and long term irreversible adverse health outcomes. Undernutrition is sometimes used synonymously with malnutrition, however, malnutrition could mean both undernutrition or overnutrition. The World Health Organization (WHO) estimates that malnutrition accounts for 54 percent of child mortality worldwide, which is about 1 million children. Another estimate, also by WHO, states that childhood underweight is the cause for about 35% of all deaths of children under the age of five worldwide.
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This article incorporates text by Marianne Sandsmark Morseth available under the CC BY-SA 3.0 license.