Differential abundance and metabolic activity of the microbiome has been linked to the onset and progression in immune and metabolic disease and oncology. Increasingly, the gut microbiome is recognized as a therapeutic intervention target, with the majority of strategies focusing on the use of Live Biotherapeutic Products (LBP) to improve outcomes. Species of gut bacteria are ecologically differentiated by their abilities to metabolize different glycans, making glycan delivery an attractive alternative modality to target the microbiome. We describe the properties and therapeutic potential of chemically diverse synthetic glycans (SGs). Fermentation of SGs by gut microbiome cultures resulted in compound-specific shifts in taxonomic and metabolite profiles not observed with reference glycans, including marketed prebiotics. Model enteric pathogens grew poorly on most SGs, potentially increasing their safety for at-risk populations. SGs increased survival, reduced weight loss, and improved clinical scores in mouse models of colitis. In a proof-of-concept study in ulcerative colitis patients we demonstrated safety and tolerability, a decreased abundance of pro-inflammatory bacteria and a decrease of fecal calprotectin, a biomarker of disease activity. Synthetic glycans are thus a promising modality to improve outcomes in immune-driven disease through selective changes to the gut microbiome.

Synthetic glycans as microbiome modulators in health and disease

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