Maternal Human Milk Oligosaccharide Profile Modulates the Impact of an Intervention with Iron and Galacto-Oligosaccharides in Kenyan Infants.

Jos Boekhorst,Sacha Schneeberger,Daniela Paganini,Guus A.M Kortman,Mary A Uyoga,Michael B Zimmermann,Simon Karanja,Thierry Hennet

doi:10.3390/nu11112596

Abstract

There is little data on human milk oligosaccharide (HMO) composition in Sub-Saharan Africa. Iron fortificants adversely affect the infant gut microbiota, while co-provision of prebiotic galacto-oligosaccharides (GOS) mitigates most of the adverse effects. Whether variations in maternal HMO profile can influence the infant response to iron and/or GOS fortificants is unknown. The aim of this study was to determine HMO profiles and the secretor/non-secretor phenotype of lactating Kenyan mothers and investigate their effects on the maternal and infant gut microbiota, and on the infant response to a fortification intervention with 5 mg iron (2.5 mg as sodium iron ethylenediaminetetraacetate and 2.5 mg as ferrous fumarate) and 7.5 g GOS. We studied mother–infant pairs (n = 80) participating in a 4-month intervention trial in which the infants (aged 6.5–9.5 months) received daily a micronutrient powder without iron, with iron or with iron and GOS. We assessed: (1) maternal secretor status and HMO composition; (2) effects of secretor status on the maternal and infant gut microbiota in a cross-sectional analysis at baseline of the intervention trial; and (3) interactions between secretor status and intervention groups during the intervention trial on the infant gut microbiota, gut inflammation, iron status, growth and infectious morbidity. Secretor prevalence was 72% and HMOs differed between secretors and non-secretors and over time of lactation. Secretor status did not predict the baseline composition of the maternal and infant gut microbiota. There was a secretor-status-by-intervention-group interaction on Bifidobacterium (p = 0.021), Z-scores for length-for-age (p = 0.022) and weight-for-age (p = 0.018), and soluble transferrin receptor (p = 0.041). In the no iron group, longitudinal prevalence of diarrhea was higher among infants of non-secretors (23.8%) than of secretors (10.4%) (p = 0.001). In conclusion, HMO profile may modulate the infant gut microbiota response to fortificant iron; compared to infants of secretor mothers, infants of non-secretor mothers may be more vulnerable to the adverse effect of iron but also benefit more from the co-provision of GOS.

Highlights

Human milk oligosaccharides (HMOs) represent the third most abundant solid milk component after lipids and lactose in human breast milk, with a concentration of 5–10 g/L and more than 200 different structures [1]
HMO profile may modulate the infant gut microbiota response to fortificant iron; compared to infants of secretor mothers, infants of non-secretor mothers may be more vulnerable to the adverse effect of iron and benefit more from the co-provision of GOS
We have recently shown that co-provision of prebiotic galacto-oligosaccharides (GOS) in iron-containing micronutrient powders (MNPs) mitigates most of the adverse effects of the iron on the infant gut microbiota and increases iron absorption [37,39]

Summary

Introduction

Human milk oligosaccharides (HMOs) represent the third most abundant solid milk component after lipids and lactose in human breast milk, with a concentration of 5–10 g/L and more than 200 different structures [1]. The HMO composition of breast milk varies between mothers, differs across geographic regions, and changes over the course of lactation [2,3,4]. HMOs with L-fucose (Fuc) residuals in α-1-2-linkage such as 2-fucosyllactose (20 FL) and lacto-N-fucopentose I (LNFPI) are only present in breast milk of women with a functional α-1-2-fucosyltransferase (FUT2) (the secretor phenotype), but are absent in breast milk of women with a homozygous mutation in the FUT2 gene (the non-secretor phenotype) [5]. Frequency of the secretor phenotype is estimated at ~80% worldwide but varies between geographical regions [3,6]. Two recent large cohort studies in the United Kingdom and Canada found no association between maternal secretor status and the overall maternal gut microbiota composition [14,15]

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