Overcoming the limited availability of human milk oligosaccharides: challenges and opportunities for research and application

Abstract

Human milk oligosaccharides (HMOs) are complex sugars highly abundant in human milk but currently not present in infant formula. Rapidly accumulating evidence from in vitro and in vivo studies, combined with epidemiological associations and correlations, suggests that HMOs benefit infants through multiple mechanisms and in a variety of clinical contexts. Until recently, however, research on HMOs has been limited by an insufficient availability of HMOs. Most HMOs are found uniquely in human milk, and thus far it has been prohibitively tedious and expensive to isolate and synthesize them. This article reviews new strategies to overcome this lack of availability by generating HMOs through chemoenzymatic synthesis, microbial metabolic engineering, and isolation from human donor milk or dairy streams. Each approach has its advantages and comes with its own challenges, but combining the different methods and acknowledging their limitations creates new opportunities for research and application with the goal of improving maternal and infant health.

Milk Glycans and Their Interaction with the Infant-Gut Microbiota

“…HMOs are an abundant component of human milk (Bode et al 2016, Petherick 2010), with approximately 5–20 g/L of unbound oligosaccharides present in mature milk (Bode 2006, Hong et al 2014, McGuire et al 2017). Surveys of different human milks have revealed tremendous structural diversity, with intricate molecular structures among and within HMO pools (Kunz et al 2000; Wu et al 2010, 2011).…”

Delactosed permeate as a dairy processing co‐product with major potential value: a review

“…Among other functions, human milk oligosaccharides (HMOs) play an important role in modulating the epithelial and immune cell responses and contribute to the maturation of the immune system and in the development of the neonatal brain and cognition functions (Bode, ; Bode et al ., ). Because they are not hydrolysed by human digestive enzymes and are fermented by colonic bacteria with the production of short‐chain fatty acids, CO 2 and H 2 , they specifically stimulate the growth and metabolism of intestinal bifidobacteria (Ganzle, ).…”

More than sugar in the milk: human milk oligosaccharides as essential bioactive molecules in breast milk and current insight in beneficial effects

“…The commercially available hMO analogs are not isolated from human milk but are the fermentation products of genetically engineered microorganisms, which include strains of E. coli and yeast (Sprenger, Baumg€ artner, and Albermann 2017). Although hMOs are natural carbohydrates that are being recognized as safe for a long time, the use of chemical-or biotechnology-based processes to produce synthesized hMOs makes it necessary to evaluate the safety of the production procedure as well as the novel compounds through a series of registration processes (Bode et al 2016).…”