Metabolomics and Milk: The Development of the Microbiota in Breastfed Infants

Abstract

Metabolomics provides a valuable strategy for describing and annotating the structures, compositions, and functions of mammalian milk. Detailed analyses of the complex components of milk have revealed an unexpected diversity of glycans consisting of oligosaccharides, glycoproteins, and glycolipids, all of which help shape the intestinal environment and in particular the intestinal microbiome of breastfed babies. Using complete and partial ensembles of glycan mixtures, the holistic principles of metabolomics analytics were leveraged for microbial screening studies. The complex glycans of human milk proved to be highly selective in their ability to support the growth of only a very rare group of enteric bacteria. These studies led to the conclusion that a signature achievement of breast milk is the development of a unique milk-oriented intestinal microbiota that results from a functional overlap of stereospecific glycan biosynthesis in maternal mammary epithelia with equally stereospecific glycosidase enzymes encoded within the genome of the commensal bacteria. Clinical evidence in support of that hypothesis has now been generated by the simultaneous administration and quantitation of the entire repertoire of glycans in the milk going in and the feces coming out of human infants. These platforms of systems biology combining separation technologies coupled to highly accurate and sensitive mass spectrometry with exhaustive library development and computational tools provide a model for success in understanding biological processes. Metabolomics is now extending that understanding of the infant microbiota and its phenotype to the role of complex glycans in the microbiota of all ages. The relentless selective pressure on the process of lactation within the mammary epithelial cell over millennia of evolution has been to nourish, protect, and support the survival of the mother infant pair. The principles that have emerged to nourish infants provide a guiding model for diet and health of all humans. The tools of metabolomics are proving successful in revealing the mechanisms behind milk’s “genius.”