Mother's Milk: A Purposeful Contribution to the Development of the Infant Microbiota and Immunity

Abstract

Breast milk is the perfect nutrition for infants, a result of millions of years of evolution. In addition to providing a source of nutrition, breast milk contains a diverse array of microbiota and myriad biologically active components that are thought to guide the infant's developing mucosal immune system. It is believed that bacteria from the mother's intestine may translocate to breast milk and dynamically transfer to the infant. Such interplay between mother and her infant is a key to establishing a healthy infant intestinal microbiome. These intestinal bacteria protect against many respiratory and diarrheal illnesses, but are subject to environmental stresses such as antibiotic use. Orchestrating the development of the microbiota are the human milk oligosaccharides (HMOs), the synthesis of which are partially determined by the maternal genotype. HMOs are thought to play a role in preventing pathogenic bacterial adhesion though multiple mechanisms, while also providing nutrition for the microbiome. Extracellular vesicles (EVs), including exosomes, carry a diverse cargo, including mRNA, miRNA, and cytosolic and membrane-bound proteins, and are readily detectable in human breast milk. Strongly implicated in cell-cell signaling, EVs could therefore may play a further role in the development of the infant microbiome. This review considers the emerging role of breast milk microbiota, bioactive HMOs, and EVs in the establishment of the neonatal microbiome and the consequent potential for modulation of neonatal immune system development.

Keywords: breast milk; breast milk microbiome; exosomes; extracellular vesicles; human milk oligosaccharides; infant microbiome; microbiome; microbiota.

Figure 1

Factors that influence maternal breast milk microbiome and proposed mechanism of how breast milk may alter the infant gut microbiome and health outcome. A myriad of environmental, genetic, and immune factors personalize a mother’s milk for delivery to her infant. Starting from the initial feeding, the breast milk microbes and human milk oligosaccharides contribute to the composition and diversity of the infant gut microbiome. The initial gut microbes may continue to promote colonization of a healthy community or an aberrant community. During the critical window of immune development, the community types may induce metabolic alterations leading to differing immune phenotypes and long-term health outcomes. SCFA, short-chain fatty acids.

Figure 2

Mechanism of action of HMO to prevent aberrant pathogen colonization. HMO may bind directly to bacteria in the gut lumen causing conformational change in bacterial binding sites and preventing binding to cell receptors; alternatively, HMO may bind directly to gut epithelial cells causing altered expression of cell receptors, which prevent pathogen binding to gut epithelial cells. HMO, human milk oligosaccharide.