UC Davis

Milk oligosaccharides are a class of carbohydrates composed of three to twenty monosaccharides, which are found in mammalian milk and other dairy products. Bioactivities, including prebiotic, anti-pathogenic, and immunomodulatory activities, as well as roles in cognition, have been ascribed to milk oligosaccharides featuring particular structural motifs. The most prevalent source of milk oligosaccharides for humans is breast milk, but a comparable source of these beneficial compounds for formula-fed infants or individuals at other life stages is not currently available. As a result, milk oligosaccharides are recent targets for addition to infant formulas and nutraceuticals. Harnessing the bioactive potential of naturally occurring milk oligosaccharides, however, is challenged by low commercial availability of human breast milk and low concentrations of similarly structured milk oligosaccharides in traditional bovine dairy streams. This dissertation presents a look into the abundances of milk oligosaccharides and their potential sources form several non-traditional angles and proposes potential alternative sources for their isolation.

Chapter I introduces bovine milk oligosaccharides, highlights the current sources for bovine milk oligosaccharide isolation and their associated challenges, and proposes the more concentrated dairy stream, delactosed permeate, as a potential new source for bovine milk oligosaccharide isolation.

Chapter II focuses on the ‘gold standard’ human milk oligosaccharides and how the concentrations of key oligosaccharides in human milk vary with lactation stage and maternal gene expression.

Building off of the foundation established in Chapters I and II, Chapters III through VI delve more in-depth into how non-human milk oligosaccharide abundances are impacted by specific factors, and how harnessing these elements may allow for improved milk oligosaccharide isolation by increasing their source concentrations.

Chapter III examines the impact of maternal diet on bovine milk oligosaccharide abundances. This study was the first to successfully demonstrate significant differences in bovine milk oligosaccharide yields with changes in dietary fiber levels.

Chapter IV takes a more in-depth look at the composition of delactosed permeate, and is the first study to quantify bovine milk oligosaccharides in this promising concentrated dairy waste stream.

Chapter V expands beyond traditional western sources of commercial milk to investigate the milk oligosaccharide profiles of all mammalian species through the compilation and analysis of five decades of published milk oligosaccharide research. A comprehensive review of milk oligosaccharide literature at this magnitude has never before been undertaken. The analysis of the compiled data revealed overarching influences of phylogeny and evolution on milk oligosaccharide profiles and allowed for the identification of non-bovine milks that feature oligosaccharide profiles with key similarities to human breastmilk that are promising potential sources for milk oligosaccharide isolation.

Finally, Chapter VI summarizes the main conclusions of the dissertation, provides perspective on the current challenges relating to milk oligosaccharide analysis, and proposes future directions for research in this field.