Influence of sulfonated and diet-derived human milk oligosaccharides on the infant microbiome and immune markers

Wesley F Zandberg,Deanna L Gibson,Alexander M Garner,Nina A Mohtarudin,Deanna M Vollman,Sara D Vicaretti,Candice Quin

doi:10.1074/jbc.ra119.011351

Wesley F Zandberg, Deanna L Gibson + Show 5 more

Open Access

https://doi.org/10.1074/jbc.ra119.011351

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Abstract

Human milk oligosaccharides (HMOs) promote the development of the neonatal intestinal, immune, and nervous systems and has recently received considerable attention. Here we investigated how the maternal diet affects HMO biosynthesis and how any diet-induced HMO alterations influence the infant gut microbiome and immunity. Using capillary electrophoresis and MS-based analyses, we extracted and measured HMOs from breast milk samples and then correlated their levels with results from validated 24-h diet recall surveys and breast milk fatty acids. We found that fruit intake and unsaturated fatty acids in breast milk were positively correlated with an increased absolute abundance of numerous HMOs, including 16 sulfonated HMOs we identified here in humans for the first time. The diet-derived monosaccharide 5-N-glycolyl-neuraminic acid (Neu5Gc) was unambiguously detected in all samples. To gain insights into the potential impact of Neu5Gc on the infant microbiome, we used a constrained ordination approach and identified correlations between Neu5Gc levels and Bacteroides spp. in infant stool. However, Neu5Gc was not associated with marked changes in infant immune markers, in contrast with sulfonated HMOs, whose expression correlated with suppression of two major Th2 cytokines, IL-10 and IL-13. The findings of our work highlight the importance of maternal diet for HMO biosynthesis and provide as yet unexplored targets for future studies investigating interactions between HMOs and the intestinal microbiome and immunity in infants.

Highlights

Human milk oligosaccharides (HMOs) promote the development of the neonatal intestinal, immune, and nervous systems and has recently received considerable attention
We found that fruit intake and unsaturated fatty acids in breast milk were positively correlated with an increased absolute abundance of numerous HMOs, including 16 sulfonated HMOs we identified here in humans for the first time
It has been hypothesized that in women, milk and dairy products would be the major dietary source of Neu5Gc and that this monosaccharide would be observed at elevated levels in the HMOs biosynthesized by women consuming cow’s milk rather than alternative, almond-based beverages

Summary

Introduction

Human milk oligosaccharides (HMOs) promote the development of the neonatal intestinal, immune, and nervous systems and has recently received considerable attention. HMOs, in contrast to lactose, are indigestible by infants [2,3,4], but they are often readily digested by bacteria present in the large intestine and colon, provided they express the requisite glycolytic enzymes [5, 6]. By providing these microbes with a nutrient source, HMOs actively promote colonization of the neonatal gastrointestinal (GI) tract [7,8,9,10,11]. This variation is correlated with pediatric infectious disease susceptibility [22] and gut microbiome diversity [23]

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