(P10-007-23) Personalized Responses of the Gut Microbiome to Dietary Glycoproteins

Objectives: A profound lack of fiber found in the western diet may be a major driver of metabolic disease. However, some dietary ingredients may have an untapped potential to increase effective fiber intake, if existing conjugated glycans can be modified to increase their bioactivity. We hypothesized that N-glycans found in four common protein sources (whey, soy, egg, and pea protein isolates) are utilized distinctly by three representative human gut microbial communities.

Methods: Fecal samples (N = 85) from healthy donors were analyzed and characterized as one of three distinct composition types. Six samples from each composition type were analyzed by shotgun metagenomic sequencing and then pooled and used to inoculate (1% v/v) an anaerobic fermentation medium with 2% (w/v; N = 3 replicates per group) one of four purified dietary glycoprotein isolates or 2% starch. This culture was fermented in vitro at 37C anaerobically and then characterized by amplicon sequencing of the V4 region of the 16S rRNA gene. Meta-transcriptomic sequencing was also used to measure microbial gene expression during fermentation. Culture growth kinetics and fermentation profiles were measured in parallel.

Results: The distinct community composition types differed in terms of their carbohydrate degradation profile (P < 0.001) and in vitro, each community type demonstrated inocula- and substrate-specific responses in terms of growth kinetics and gene expression. The relative abundance of bacteria also demonstrated significant differences between the starting microbiome compositions and between the distinct glycoprotein sources.

Conclusions: These findings identify distinct glycan utilization across gut microbiome compositions and dietary glycoprotein sources. We conclude that differences in glycan architecture across protein sources and differences in carbohydrate active enzyme repertoires lead to distinct strategies for glycan metabolism, depending on an individual’s gut microbiome.

Funding Sources: This work was supported by the USDA National Institute of Food and Agriculture, #2022-67018-36233 and by funding from the National Institute of General Medical Sciences (GM103440 and GM104944) from the National Institutes of Health, via Nevada INBRE.