Fecal metatranscriptomics and glycomics suggests that bovine milk oligosaccharides are fully utilized by healthy adults

Authors: WESTREICH, SAMUEL - University Of California, Davis; SALCEDO, JAIME - University Of California, Davis; DURBIN-JOHNSON, BLYTHE - University Of California, Davis; SMILOWITZ, JENNIFER - University Of California, Davis; KORF, IAN - University Of California, Davis; MILLS, DAVID - University Of California, Davis; DANIELA, BARILE - University Of California, Davis; Lemay, Danielle

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/3/2020
Publication Date: 1/17/2020
Citation: Westreich, S.T., Salcedo, J., Durbin-Johnson, B., Smilowitz, J.T., Korf, I., Mills, D.A., Daniela, B., Lemay, D.G. 2020. Fecal metatranscriptomics and glycomics suggests that bovine milk oligosaccharides are fully utilized by healthy adults. Journal of Nutritional Biochemistry. 79. https://doi.org/10.1016/j.jnutbio.2020.108340.
DOI: https://doi.org/10.1016/j.jnutbio.2020.108340

Interpretive Summary: Complex oligosaccharides found in human milk play a vital role in the growth of microbial populations in the human infant. Bovine milk oligosaccharides (BMO) have similar structures, but have not been studied for their effects on the gut microbiome of healthy adults. We therefore used a new sequencing and analysis method—metatranscriptomics—to observe all genes expressed by all organisms in the stool of humans fed BMO supplements. We found that fecal microbes expressed genes that could be involved in fermenting BMO. However, they did not change in response to the BMO supplement. Importantly, these BMO-fermenting genes were expressed even in samples from humans exposed only to placebo, suggesting that the microbiomes of healthy adults actively express genes that readily ferment BMO. We additionally used a new technique—glycomics—to directly measure the amount of BMO in the stool. Intact BMO in the stool of BMO-supplemented participants was not different from placebo. These pieces of evidence collectively suggest that the BMO is fully fermented higher in the gastrointestinal tract. Further studies will be needed to determine the health effects of this readily fermentable prebiotic.

Technical Abstract: Complex oligosaccharides found in human milk play a vital role in gut microbiome development for the human infant. Bovine milk oligosaccharides (BMO) have similar structures with those derived from human milk, but their fate in the digestive tract of healthy adult consumers is unknown. Healthy human subjects consumed two BMO doses over 11 day periods each and provided fecal samples. Metatranscriptomics of fecal samples was conducted to determine microbial and host gene expression in response to the supplement. Fecal samples were also analyzed by mass spectrometry to determine levels of undigested BMO. No changes were observed in microbial gene expression across all participants. Repeated sampling enabled subject-specific analyses: four of six participants had minor, yet statistically significant, changes in microbial gene expression. No significant change was observed in the gene expression of host cells exfoliated in stool. Levels of BMO excreted in feces after supplementation were not significantly different from placebo and were not correlated with dosage or expressed microbial enzyme levels. Collectively, these data suggest that BMO is fully fermented in the human gastrointestinal tract upstream of the distal colon. Additionally, the unaltered host transcriptome provides further evidence for the safety of BMO as a dietary supplement or food ingredient. Further research is needed to investigate potential health benefits of this completely fermentable prebiotic that naturally occurs in cow’s milk.