Supplementation With Lactoferrin and Lysozyme Ameliorates Environmental Enteric Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Trial

Abstract

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.

Antibacterial and Anti‐biofilm Activity of the Human Breast Milk Glycoprotein Lactoferrin against Group B Streptococcus

“…While some benefits have been observed with bovine lactoferrin supplementation, even more success has been shown when lactoferrin is used in combination with other biological agents. For instance, children supplemented with lactoferrin and lysozyme, another component of breast milk observed to improve gut health, experienced decreased hospitalization and reduced development of acute malnutrition [48] . In another study with lactoferrin in combination with Lactobacillus GG, infants with intervention showed a decreased incidence of severe necrotizing enterocolitis [49] .…”

Environmental enteric dysfunction: a review of potential mechanisms, consequences and management strategies

“…Identifying components of breast milk that protect children from diarrhea in the first six-months of life may offer the opportunity to supplement beyond this period and provide extended protection to older children. A recently published study of bovine and recombinant human lactoferrin and lysozyme reported no significant effect on lactulose excretion [53]. However, the intervention did reduce the incidence of malnutrition and hospitalization in the included children.…”

Lactoferrin Reverses Methotrexate Driven Epithelial Barrier Defect by Inhibiting TGF-β Mediated Epithelial to Mesenchymal Transition

“…In addition, lactoferrin has demonstrated the capacity to protect from methotrexate induced barrier dysfunction in rats 26 . Particularly intriguing is a recent report that suggests that lactoferrin improves barrier function in the context of environmental enteropathy 27 .…”