New insights into environmental enteric dysfunction

Trehan, Indi; Kelly, Paul; Shaikh, Nurmohammad; Manary, Mark J.

doi:10.1136/archdischild-2015-309534

Cited by 41 publications

(38 citation statements)

References 35 publications

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“…Environmental enteric dysfunction (EED), an asymptomatic condition characterized by chronic inflammation of the duodenum and jejunum and abnormal gut permeability, is widespread among children under five years of age in developing countries (Trehan et al, 2016). EED is associated with growth failure, oral vaccine failure, impaired absorption of nutrients, and high morbidity and mortality.…”

Section: Introductionmentioning

confidence: 99%

“…The diet of children at risk for EED is generally of poor quality, being low in animal source foods, essential amino acids, choline, essential fatty acids, and micronutrients (Krebs et al, 2014, Semba et al, 2016a, Semba et al, 2016c, Watanabe and Petri, 2016). Clinical trials to ameliorate EED involving various supplements, antibiotics, anti-inflammatory agents, and improvement in hygiene have been disappointing (Crane et al, 2015, Trehan et al, 2016). To date, interventions have been based upon an incomplete understanding of the pathogenesis of EED.…”

Section: Introductionmentioning

confidence: 99%

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Environmental Enteric Dysfunction is Associated with Carnitine Deficiency and Altered Fatty Acid Oxidation

Semba

Trehan

et al. 2017

EBioMedicine

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BackgroundEnvironmental enteric dysfunction (EED), a condition characterized by small intestine inflammation and abnormal gut permeability, is widespread in children in developing countries and a major cause of growth failure. The pathophysiology of EED remains poorly understood.MethodsWe measured serum metabolites using liquid chromatography-tandem mass spectrometry in 400 children, aged 12–59 months, from rural Malawi. Gut permeability was assessed by the dual-sugar absorption test.Findings80.7% of children had EED. Of 677 serum metabolites measured, 21 were negatively associated and 56 were positively associated with gut permeability, using a false discovery rate approach (q < 0.05, p < 0.0095). Increased gut permeability was associated with elevated acylcarnitines, deoxycarnitine, fatty acid β-oxidation intermediates, fatty acid ω-oxidation products, odd-chain fatty acids, trimethylamine-N-oxide, cystathionine, and homocitrulline, and with lower citrulline, ornithine, polyphenol metabolites, hippurate, tryptophan, and indolelactate.InterpretationEED is a syndrome characterized by secondary carnitine deficiency, abnormal fatty acid oxidation, alterations in polyphenol and amino acid metabolites, and metabolic dysregulation of sulfur amino acids, tryptophan, and the urea cycle. Future studies are needed to corroborate the presence of secondary carnitine deficiency among children with EED and to understand how these metabolic derangements may negatively affect the growth and development of young children.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Environmental Enteric Dysfunction is Associated with Carnitine Deficiency and Altered Fatty Acid Oxidation

Semba

Trehan

et al. 2017

EBioMedicine

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“…A number of hypotheses have been put forward to explain the differences in efficacy and vaccineelicited immunity between HIC and LMIC. The hypotheses include (i) maternal factors (such as interference from transplacental antibodies and antibody and nonantibody breast milk components [13,[19][20][21][22][23]), (ii) coadministration with the oral polio vaccine (24-27), (iii) concurrent infection with other enteric pathogens (28), (iv) micronutrient or protein-energy malnutrition (29-31), (v) effects of environmental enteropathy or dysbiosis of the gut microbiome (32)(33)(34)(35)(36)(37), and (vi) host genetic factors (histo-blood group antigens [38,39]). A better understanding of these factors which decrease the efficacy of RV in LMIC may help to inform interventions to improve efficacy and to further reduce the number of child deaths due to rotavirus disease.…”

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confidence: 99%

Contribution of Maternal Immunity to Decreased Rotavirus Vaccine Performance in Low- and Middle-Income Countries

Mwila

Chilengi

Simuyandi

et al. 2017

Clin Vaccine Immunol

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The role of maternal immunity, received by infants either transplacentally or orally from breast milk, in rotavirus vaccine (RV) performance is evaluated here. Breastfeeding withholding has no effect on vaccine responses, but higher levels of transplacental rotavirus-specific IgG antibody contribute to reduced vaccine seroconversion. The gaps in knowledge on the factors associated with low RV efficacy in low-and middle-income countries (LMIC) remain, and further research is needed to shed more light on these issues. KEYWORDS immunization, low-and middle-income countries, maternal, rotavirus D espite the progress seen with the global introduction of rotavirus vaccines (RV), diarrhea is still a leading cause of death in children under the age of 5 years, and a substantial proportion of disease cases are still attributable to rotavirus infection. The latest estimates show that approximately 215,000 children die each year from rotavirusassociated diarrhea, and approximately 56% of these deaths are in sub-Saharan Africa (1). The World Health Organization (WHO) recommended the introduction of oral RV into national immunization programs (2), and many countries have heeded this call. As of September 2016, the WHO lists 86 countries as having included RV in their national immunization programs, and 6 more are in the course of doing so in 2016 (www.who.int/immunization/monitoring_surveillance/VaccineIntroStatus.pptx). Approximately 50% of the countries in Africa and Asia, over 80% of those in North America, South America, and Australia, and approximately 40% of those in Europe have introduced RV. Following RV introduction, there was a notable reduction in the number of deaths due to diarrhea (1). However, there is consistent evidence from clinical trials that RV have lower efficacies in low-and middle-income countries (LMIC): vaccine efficacies are 80 to 90% in high-income countries (HIC) and 40 to 60% in LMIC (3-8). Indeed, there is growing evidence from vaccine effectiveness studies emerging from the field that in real-life use, vaccine effectiveness is also consistently lower in LMIC (9-12).In addition to the differences in observed vaccine efficacy and effectiveness, there are also marked differences in vaccine-elicited immunity as reported by various vaccine-elicited antibody titers following rotavirus immunization (13)(14)(15)(16)(17)(18). A number of hypotheses have been put forward to explain the differences in efficacy and vaccineelicited immunity between HIC and LMIC. The hypotheses include (i) maternal factors (such as interference from transplacental antibodies and antibody and nonantibody breast milk components [13,[19][20][21][22][23] [38,39]). A better understanding of these factors which decrease the efficacy of RV in LMIC may help to inform interventions to improve efficacy and to further reduce the number of child deaths due to rotavirus disease. This review examines the correlations between maternal immune factors and RV responses and their potential effect on vaccine efficacy. NATURAL ROTAVIRUS...

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“…Even after discharge, children have a poor prognosis, with 42% mortality over the subsequent year [45]. In our experience, it is a subgroup of children with SAM and persistent diarrhoea who pose the most difficult management challenges, although the vast majority of children with SAM have a degree of enteropathy [44, 46]. Indeed, the intimate relationship between malnutrition and a ‘chronic derangement of the alimentary canal’ was described among the British poor in 1868 [47].…”

Section: Malnutrition Enteropathymentioning

confidence: 99%

Tropical Enteropathies

Louis-Auguste

Kelly

2017

Curr Gastroenterol Rep

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Purpose of ReviewThe term ‘tropical enteropathy’ originated in observations in the 1960s that small intestinal morphology and function differed in the tropics from the norms found in temperate climates. It was subsequently shown that this enteropathy is more closely related to environmental conditions than latitude, and it was re-labelled ‘environmental enteropathy’. It is now recognised that environmental enteropathy (also now called environmental enteric dysfunction) has implications for the health and linear growth of children in low- and middle-income countries, and it may underlie poor responses to oral vaccination in these countries. The purpose of this review is to define and clarify this enteropathy despite the confusing terminology it has attracted and to contrast it with other enteropathic states.Recent FindingsRecent work has begun to demonstrate the nature of the mucosal lesion and the relationship with microbial translocation which is currently thought to link a failure of mucosal barrier function and the cascade of systemic inflammation which inhibits growth. The evidence is still correlative rather than definitive, but derives some additional support from animal models. There are some common features between environmental enteropathy and other enteropathies, but there are important differences also. The mechanism of the link between enteropathy and vaccine failure is not understood, and neither is it clear how the more severe form of enteropathy, which we refer to as malnutrition enteropathy, is driven by nutrient depletion and intestinal infection.SummaryTropical enteropathies form a group of disorders which include environmental and nutritional enteropathies. The long-term health implications of these disorders for health in low-income countries are just being explored, but the scale of their effects is very large, with millions of people affected.

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New insights into environmental enteric dysfunction

Cited by 41 publications

References 35 publications

Environmental Enteric Dysfunction is Associated with Carnitine Deficiency and Altered Fatty Acid Oxidation

Environmental Enteric Dysfunction is Associated with Carnitine Deficiency and Altered Fatty Acid Oxidation

Contribution of Maternal Immunity to Decreased Rotavirus Vaccine Performance in Low- and Middle-Income Countries

Tropical Enteropathies

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