ABSTRACT
BACKGROUND: A staggering 99% of infant undernutrition mortality comes from Sub-Saharan Africa and South Asia. Despite multiple interventions focusing on nutrition adequacy, 2.7 million children worldwide remain associated with undernutrition-related mortality. The lack of impact from multiple interventions toward undernutrition reflects a strong reason to believe that EED is the missing link that sustains undernutrition in low-to-middle-income countries (LMICs). EED is a sub-clinical condition caused by repeated oral enteropathogenic and non-pathogenic fecal microbes exposure that causes intestinal villous malformation, multi-omics changes, chronic intestinal and systemic inflammation, and gut dysbiosis. EED impacts the absorptive capacity and the integrity of the gut, causing a cycle of undernutrition in children. There is currently no protocol for the diagnosis and treatment of EED, hence EED is widely believed to be highly prevalent and underdiagnosed in LMICs. OBJECTIVE: To our knowledge, this is the first systematic review to study the impact of nutritional interventions on EED. Previous studies yielded inconsistent results, hence the synthesis of this information is essential in attaining a deeper understanding of EED to formulate new targets of intervention against child undernutrition. METHODS: This systematic review is registered to PROSPERO (CRD42022363157) in accordance to PRISMA, using keywords referring to nutrient supplementation, EED, and child growth failure. RESULTS: Eleven articles were eligible for review, comprising randomized controlled trials performed mainly in the African continent, with a total of 5689 healthy children eligible for analysis. CONCLUSION: The systematic review illustrates that nutritional interventions have a minimal impact on EED biomarkers and linear growth and reflects the importance of understanding better the mechanisms causing EED and its consequences. It appears that the anabolic contribution of nutrition intervention to child growth is negated by EED.
Subject(s)
Dietary Supplements , Rural Population , Humans , Infant , Child , Intestinal Diseases/therapy , Intestinal Diseases/physiopathologyABSTRACT
ABSTRACT Background: A staggering 99% of infant undernutrition mortality comes from Sub-Saharan Africa and South Asia. Despite multiple interventions focusing on nutrition adequacy, 2.7 million children worldwide remain associated with undernutrition-related mortality. The lack of impact from multiple interventions toward undernutrition reflects a strong reason to believe that EED is the missing link that sustains undernutrition in low-to-middle-income countries (LMICs). EED is a sub-clinical condition caused by repeated oral enteropathogenic and non-pathogenic fecal microbes exposure that causes intestinal villous malformation, multi-omics changes, chronic intestinal and systemic inflammation, and gut dysbiosis. EED impacts the absorptive capacity and the integrity of the gut, causing a cycle of undernutrition in children. There is currently no protocol for the diagnosis and treatment of EED, hence EED is widely believed to be highly prevalent and underdiagnosed in LMICs. Objective: To our knowledge, this is the first systematic review to study the impact of nutritional interventions on EED. Previous studies yielded inconsistent results, hence the synthesis of this information is essential in attaining a deeper understanding of EED to formulate new targets of intervention against child undernutrition. Methods: This systematic review is registered to PROSPERO (CRD42022363157) in accordance to PRISMA, using keywords referring to nutrient supplementation, EED, and child growth failure. Results: Eleven articles were eligible for review, comprising randomized controlled trials performed mainly in the African continent, with a total of 5689 healthy children eligible for analysis. Conclusion: The systematic review illustrates that nutritional interventions have a minimal impact on EED biomarkers and linear growth and reflects the importance of understanding better the mechanisms causing EED and its consequences. It appears that the anabolic contribution of nutrition intervention to child growth is negated by EED.
RESUMO Contexto: Um número impressionante de 99% da mortalidade por desnutrição infantil provém da África Subsaariana e do Sul da Ásia. Apesar de múltiplas intervenções focadas na adequação nutricional, 2,7 milhões de crianças em todo o mundo permanecem associadas à mortalidade relacionada à desnutrição. A falta de impacto de múltiplas intervenções em direção à desnutrição reflete uma forte razão para acreditar que a disfunção entérica ambiental (DEA) é o elo perdido que sustenta a desnutrição em países de baixa e média renda. A DEA é uma condição subclínica causada pela exposição repetida a micróbios fecais enteropatogênicos e não patogênicos por via oral, que causa malformação vilosa intestinal, alterações multiômicas, inflamação intestinal e sistêmica crônica, e disbiose intestinal. A DEA impacta a capacidade absortiva e a integridade do intestino, causando um ciclo de desnutrição em crianças. Atualmente, não existe protocolo para o diagnóstico e tratamento da DEA, portanto, acredita-se amplamente que a DEA seja altamente prevalente e subdiagnosticada em países de baixa e média renda. Objetivo: Até onde sabemos, esta é a primeira revisão sistemática para estudar o impacto das intervenções nutricionais na DEA. Estudos anteriores apresentaram resultados inconsistentes, portanto, a síntese dessas informações é essencial para obter uma compreensão mais profunda da DEA e formular novos alvos de intervenção contra a desnutrição infantil. Métodos: Esta revisão sistemática está registrada no PROSPERO (CRD42022363157) de acordo com o PRISMA, utilizando palavras-chave referentes à suplementação de nutrientes, DEA e falha no crescimento infantil. Resultados: Onze artigos foram elegíveis para revisão, compreendendo ensaios clínicos randomizados realizados principalmente no continente africano, com um total de 5689 crianças saudáveis elegíveis para análise. Conclusão: A revisão sistemática ilustra que as intervenções nutricionais têm um impacto mínimo nos biomarcadores da DEA e no crescimento linear, e reflete a importância de entender melhor os mecanismos que causam a DEA e suas consequências. Parece que a contribuição anabólica da intervenção nutricional para o crescimento infantil é negada pela DEA.