RESUMO
INTRODUCTION: Environmental enteric dysfunction (EED) predisposes children throughout the developing world to high rates of systemic exposure to enteric pathogens and stunting. Effective interventions that treat or prevent EED may help children achieve their full physical and cognitive potential. The objective of this study is to test whether 2 components of breast milk would improve a biomarker of EED and linear growth during the second year of life. METHODS: A prospective, randomized, double-blind, placebo-controlled clinical trial among children aged 12-23 months was conducted in rural Malawi. The experimental group received a daily supplement of 1.5 g of lactoferrin and 0.2 g of lysozyme for 16 weeks. The primary outcome was an improvement in EED, as measured by the change in the percentage of ingested lactulose excreted into the urine (Δ%L). RESULTS: Among 214 children who completed the study, there was a significant difference in Δ%L between the control and experimental groups over 8 weeks (an increase of 0.23% vs 0.14%, respectively; P = 0.04). However, this relative improvement was not as strongly sustained over the full 16 weeks of the study (an increase of 0.16% vs 0.11%, respectively; P = 0.17). No difference in linear growth over this short period was observed. The experimental intervention group had significantly lower rates of hospitalization and the development of acute malnutrition during the course of the study (2.5% vs 10.3%, relative risk 0.25; P < 0.02). DISCUSSION: Supplementation with lactoferrin and lysozyme in a population of agrarian children during the second year of life has a beneficial effect on gut health. This intervention also protected against hospitalization and the development of acute malnutrition, a finding with a significant clinical and public health importance. This finding should be pursued in larger studies with longer follow-up and optimized dosing.
Assuntos
Transtornos do Crescimento/prevenção & controle , Transtornos da Nutrição do Lactente/tratamento farmacológico , Lactoferrina/uso terapêutico , Desnutrição/tratamento farmacológico , Muramidase/uso terapêutico , Espru Tropical/tratamento farmacológico , Desenvolvimento Infantil , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Malaui , Masculino , Estudos ProspectivosAssuntos
Golfe , Queimadura Solar , Humanos , Luz Solar , Protetores Solares/uso terapêutico , Raios UltravioletaRESUMO
Recent studies have suggested that environmental enteric dysfunction can be assessed in rural African children by measuring levels of fecal mRNA transcripts. The field collection of fecal samples is less invasive and cumbersome than administration of the lactulose:mannitol test, which is typically used to assess environmental enteric dysfunction. This study sought to determine if, as in children aged 12-60 months, an array of seven fecal host transcripts (CD53, CDX1, HLA-DRA, TNF, S100A8, MUC12, and REG1A) could predict environmental enteric dysfunction in rural African infants. Host fecal transcript abundance was correlated to the percentage of lactulose (%L) excreted in the urine for 340 samples from Malawian children aged 6-12 months. Permeability was categorized as not severe (%L < 0.45) and severe (%L ≥ 0.45). This study found the prevalence of severe environmental enteric dysfunction to be 114/834 (14%), lower than what was previously reported for 12-60 months old children, 595/1521 (39%, P = 0.001). In linear regression analysis with the seven host transcripts, two were associated with %L: ß coefficients of -1.843 ( P = 0.035) and 0.215 ( P = 0.006) for CDX1 and REG1A, respectively. The seven fecal host transcripts in a random forest model did not predict severe environmental enteric dysfunction. Future models utilizing different transcripts identified from an untargeted, agnostic assessment of all potential host transcripts could provide accurate predictions of environmental enteric dysfunction in infants. Impact statement Environmental enteric dysfunction (EED) is associated with reduced linear growth. The dual sugar absorption test has been used as a non-invasive method to determine the gut health of individuals. Alternative methods using fecal host mRNAs as predictors of the gut health are promising. In older children, we have determined that seven transcripts can predict the gut health in a random forest model. Our current study determined that the host fecal mRNA is abundant in infants and toddlers alike. Severe EED in rural Malawian children is less prevalent in infants than in young children. REG1A and CDX1 are associated with gut health. Fecal host mRNA may well be a means to assess gut health in African infants, but the panel of transcripts used to do this will differ from that in older children.
Assuntos
Fezes , Mucosa Intestinal/patologia , RNA Mensageiro/metabolismo , Gastropatias/patologia , Biomarcadores/metabolismo , Criança , Pré-Escolar , Feminino , Perfilação da Expressão Gênica , Humanos , Lactente , Malaui , Masculino , Permeabilidade , Reação em Cadeia da Polimerase , População Rural , Gastropatias/diagnóstico , Gastropatias/genética , Transcriptoma , UrinaRESUMO
BACKGROUND: Chronic childhood malnutrition, as manifested by stunted linear growth, remains a persistent barrier to optimal child growth and societal development. Environmental enteric dysfunction (EED) is a significant underlying factor in the causal pathway to stunting, delayed cognitive development, and ultimately morbidity and mortality. Effective therapies against EED and stunting are lacking and further clinical trials are warranted to effectively identify and operationalize interventions. METHODS/DESIGN: A prospective randomized placebo-controlled parallel-group randomized controlled trial will be conducted to determine if a daily supplement of lactoferrin and lysozyme, two important proteins found in breast milk, can decrease the burden of EED and stunting in rural Malawian children aged 12-23 months old. The intervention and control groups will have a sample size of 86 subjects each. All field and laboratory researchers will be blinded to the assigned intervention group, as will the subjects and their caregivers. The percentage of ingested lactulose excreted in the urine (Δ%L) after 4 h will be used as the biomarker for EED and linear growth as the measure of chronic malnutrition (stunting). The primary outcomes of interest will be change in Δ%L from baseline to 8 weeks and to 16 weeks. Intention-to-treat analyses will be used. DISCUSSION: A rigorous clinical trial design will be used to assess the biologically plausible use of lactoferrin and lysozyme as dietary supplements for children at high risk for EED. If proven effective, these safe proteins may serve to markedly reduce the burden of childhood malnutrition and improve survival. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02925026 . Registered on 4 October 2016.