Tolerability and safety of the intake of bovine milk oligosaccharides extracted from cheese whey in healthy human adults

Abstract

Mechanistic research suggests a unique evolutionary relationship between complex milk oligosaccharides and cognate bifidobacteria enriched in breast-fed infants. Bovine milk oligosaccharides (BMO) were recently identified as structurally and functionally similar to human milk oligosaccharides. The present single-blind three-way crossover study is the first to determine the safety and tolerability of BMO consumption by healthy human participants (n 12) and its effects on faecal microbiota and microbial metabolism. Participants consumed each supplement (placebo-control; low- and high-BMO doses) for eleven consecutive days, followed by a 2-week washout period prior to initiating the next supplement arm. Low and high BMO doses were consumed as 25 and 35 % of each individual's daily fibre intake, respectively. Safety and tolerability were measured using standardised questionnaires on gut and stomach discomfort and stool consistency. Faecal extracts were profiled for bacterial populations by next-generation sequencing (NGS) and bifidobacteria presence was confirmed using quantitative PCR. Urine was analysed for changes in microbial metabolism using nuclear magnetic resonance spectroscopy (1H-NMR). Consumption of both the low and high BMO doses was well tolerated and did not change stool consistency from baseline. Multivariate analysis of the NGS results demonstrated no change in faecal microbiota phyla among the placebo-control and BMO supplement groups. In conclusion, BMO supplementation was well tolerated in healthy adults and has the potential to shift faecal microbiota toward beneficial strains as part of a synbiotic treatment with probiotic cultures that selectively metabolise oligosaccharides.

Structures and Metabolic Properties of Bovine Milk Oligosaccharides and Their Potential in the Development of Novel Therapeutics

“…Future studies will likely probe further into the mechanistic details of OS functionalities, as well as evaluate the feasibility of supplementing these molecules into adult diets as therapeutics. The safety and tolerability of isolated milk OS for human consumption were recently evaluated in two independent studies and showed promising results, with even relatively high dosages being well-tolerated (76, 77). These studies could pave the way for the known metabolic impacts of BMOs to be further evaluated in human subjects, including in specialized applications such as infant formula production.…”

Milk Glycans and Their Interaction with the Infant-Gut Microbiota

“…A recent clinical study showed that consumption of BMOs by adult volunteers was remarkably well-tolerated, even at dosages of up to 35% of daily fiber intake (Smilowitz et al 2017). Additional studies have provided some mechanistic insight into possible benefits of BMO.…”

Structure and Function of Bovine Whey Derived Oligosaccharides Showing Synbiotic Epithelial Barrier Protective Properties

“…Bovine milk and whey oligosaccharide fractions were identified as potentially interesting prebiotics, as they contain functional oligosaccharides such as sialyllactoses, galactosyllactoses and N-acetylgalactosyllactose [ 32 , 33 , 34 ]. However, bovine milk contains relatively small amounts of oligosaccharides, making their enrichment for nutritional applications challenging.…”