Human milk oligosaccharides: Shaping the infant gut microbiota and supporting health

Abstract

Human milk oligosaccharides (HMO) are complex sugars which are found in breast milk at significant concentrations and with unique structural diversity. These sugars are the fourth most abundant component of human milk after water, lipids, and lactose and yet provide no direct nutritional value to the infant. Recent research has highlighted that HMOs have various functional roles to play in infant development. These sugars act as prebiotics by promoting growth of beneficial intestinal bacteria thereby generating short-chain fatty acids which are critical for gut health. HMOs also directly modulate host-epithelial immune responses and can selectively reduce binding of pathogenic bacteria and viruses to the gut epithelium preventing the emergence of a disease. This review covers current knowledge related to the functional biology of HMOs and their associated impact on infant gut health.

Keywords: Breast milk; Gut health; Human milk oligosaccharides; Prebiotics.

Graphical abstract

Fig. 1

Schematic summary of the beneficial roles human milk oligosaccharides (HMOs) play in the digestive tract of breast fed infants. 1) HMOs have been shown to act as antivirals and antimicrobials by binding to pathogens and toxins and by directly binding to epithelial receptors. Adhesion and infection by invading pathogens is subsequently blocked. HMOs also prevent viral uptake by binding C-lectin receptors on dendritic cells (DCs) 2) HMOs serve as prebiotic agents, selectively enriching bifidogenic gut bacteria. This confers a selective advantage to bifidobacterial species over pathogens, providing further protection against infectious disease. Metabolites produced during microbial fermentation of HMO have a role to play in developmental physiology of infants. 3) Short chain fatty acids (SCFAs), which are the major metabolites of HMO fermentation, have been shown to influence maturation of intestinal epithelial cells (IECs). HMOs improve barrier function by modulating expression of tight junction proteins, thereby reducing permeability of the intestinal barrier. Expression of proteins at the glycocalyx and mucus layers is also altered by HMOs and HMO metabolites. 4) HMOs interact with immune cells (DCs, T Cells, B Cells) and affect expression of pro/ anti-inflammatory cytokines. HMOs thereby play a role in maintaining immune homeostasis.