muramidase and Growth-Disorders

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.. 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).. 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).. 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.

Topics: Child Development; Dietary Supplements; Double-Blind Method; Female; Growth Disorders; Humans; Infant; Infant Nutrition Disorders; Infant Nutritional Physiological Phenomena; Lactoferrin; Malawi; Male; Malnutrition; Muramidase; Prospective Studies; Sprue, Tropical

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.. 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.. 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.. Clinicaltrials.gov, NCT02925026 . Registered on 4 October 2016.

Topics: Age Factors; Body Height; Child Development; Clinical Protocols; Dietary Supplements; Female; Growth Disorders; Humans; Infant; Infant Nutrition Disorders; Infant Nutritional Physiological Phenomena; Intention to Treat Analysis; Lactoferrin; Malawi; Male; Malnutrition; Muramidase; Nutritional Status; Prospective Studies; Research Design; Sprue, Tropical; Time Factors; Treatment Outcome

Individuals with postnatal growth retardation (PGR) are prone to developing chronic diseases. Abnormal development in small intestine is casually implicated in impaired growth. However, the exact mechanism is still implausible. In this present study, PGR piglets (aged 42 days) were employed as a good model to analyze developmental changes in intestinal mucosal barrier function. Our data demonstrated that PGR piglets exhibited impaired jejunal and ileal epithelial villous morphology and permeability, accompanied by decreased cell proliferation ability and increased apoptosis rate. In addition, the expression of tight junction proteins (ZO-1, claudin 1, and occludin) and E-cadherin was markedly inhibited by PGR. The expression of P-glycoprotein was significantly reduced in PGR piglets, as well as decreased activity of lysozyme. Moreover, the mRNA abundance and content of inflammatory cytokines were significantly increased in the intestinal mucosa and plasma of PGR piglets, respectively. PGR also contributed to lower level of sIgA, and higher level of CD68-positive rate, β-defensins, and protein expression involved p38 MAPK/NF-κB pathway. Furthermore, PGR altered the intestinal microbial community such as decreased genus Alloprevotella and Oscillospira abundances, and led to lower microbial-derived butyrate production, which may be potential targets for treatment. Collectively, our findings indicated that the intestinal mucosal barrier function of PGR piglets could develop the nutritional intervention strategies in prevention and treatment of the intestinal mucosal barrier dysfunction in piglets and humans.

Topics: Animals; Animals, Newborn; Apoptosis; ATP Binding Cassette Transporter, Subfamily B, Member 1; Bacteria; Butyrates; Cell Proliferation; Cytokines; Disease Models, Animal; Gastrointestinal Microbiome; Growth Disorders; Inflammation Mediators; Intestinal Mucosa; Intestine, Small; Muramidase; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Permeability; Sus scrofa; Tight Junction Proteins