Gold standard for nutrition: a review of human milk oligosaccharide and its effects on infant gut microbiota

Abstract

Human milk is the gold standard for nutrition of infant growth, whose nutritional value is mainly attributed to human milk oligosaccharides (HMOs). HMOs, the third most abundant component of human milk after lactose and lipids, are complex sugars with unique structural diversity which are indigestible by the infant. Acting as prebiotics, multiple beneficial functions of HMO are believed to be exerted through interactions with the gut microbiota either directly or indirectly, such as supporting beneficial bacteria growth, anti-pathogenic effects, and modulation of intestinal epithelial cell response. Recent studies have highlighted that HMOs can boost infants health and reduce disease risk, revealing potential of HMOs in food additive and therapeutics. The present paper discusses recent research in respect to the impact of HMO on the infant gut microbiome, with emphasis on the molecular basis of mechanism underlying beneficial effects of HMOs.

Keywords: Bifidobacterium; Human milk; Human milk oligosaccharides (HMOs); Infant formula; Infant gut microbiota; Oligosaccharides (OS); Prebiotics.

Fig. 1

Structures of main HMOs. HMO is made up of five basic units: Sia, GlcNAc, Fuc, Gal, and Glc [28]. All HMOs contain a lactose core which can be further lengthened by LNB (type-1 chain) or N-acetyllactosamine (type-2 chain) via either β1–3 or β1–6 linkage [30]. Based on the core HMO structures are sialylated and/or fucosylated, they can be mainly classified into three groups: FucOS, SiaOS, and neutral OS [30]. Structures of the main HMO are showed

Fig. 2

Four phenotypes of FucOS were produced by Se and Le genes [41, 44]. Se and Le genes play an important role in determining the composition of FucOS [34]. FUT2 is encoded by the first gene whereas FUT3 is encoded by the second one [–43]. According to the activation state of genes, mothers can be classified as either positive (+) or negative (−) for both genes, where 70% are Se(+)Le(+), 20% Se(−)Le(+), 9% Se(+)Le(−), and 1% Se(−)Le(−) [, –47], and phenotypes to production of FucOS and main FucOS synthesized are showed

Fig. 3

Schematic summary of main effects of HMOs. A HMOs stimulate growth of beneficial bactria, such as Bififidobacteria, and inhibit growth of harmful bacteria to regulate gut microbiota composition [132]. B HMOs serve as pathogen binding decoy receptors to prevent pathogens from binding to epithelial cell receptors [149]. C HMOs alter glycocalyx [171], influence epithelial cell proliferation [168] and modulate tight junction protein expression [167], thereby reducing permeability of the gut barrier