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Abstract
Relative abundances of bacterial species in the gut microbiome have been linked to many diseases. Species of gut bacteria are ecologically differentiated by their abilities to metabolize different glycans, making glycan delivery a powerful way to alter the microbiome to promote health. Here, we study the properties and therapeutic potential of chemically diverse synthetic glycans (SGs). Fermentation of SGs by gut microbiome cultures results in compound-specific shifts in taxonomic and metabolite profiles not observed with reference glycans, including prebiotics. Model enteric pathogens grow poorly on most SGs, potentially increasing their safety for at-risk populations. SGs increase survival, reduce weight loss, and improve clinical scores in mouse models of colitis. Synthetic glycans are thus a promising modality to improve health through selective changes to the gut microbiome.
Here, the authors characterize the gut microbiome fermentation properties and therapeutic potential of chemically diverse synthetic glycans (SGs), showing they promote specific shifts in taxonomic and metabolite profiles, and exhibit therapeutic benefits in mouse models of colonic inflammation, together implying SGs as a potential avenue to treat disease by modulating the composition and metabolites produced by the gut microbiome.
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1 Kaleido Biosciences, Lexington, USA
2 Kaleido Biosciences, Lexington, USA; Seres Therapeutics, Cambridge, USA (GRID:grid.511699.3) (ISNI:0000 0004 6487 6327)
3 Kaleido Biosciences, Lexington, USA (GRID:grid.511699.3)
4 Kaleido Biosciences, Lexington, USA (GRID:grid.511699.3); Pareto Bio, Cambridge, USA (GRID:grid.511699.3)
5 glyXera GmbH, Magdeburg, Germany (GRID:grid.511699.3)
6 glyXera GmbH, Magdeburg, Germany (GRID:grid.511699.3); Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany (GRID:grid.419517.f) (ISNI:0000 0004 0491 802X)
7 Kaleido Biosciences, Lexington, USA (GRID:grid.419517.f); Inc and Morningside BioPharma Advisory, Bacainn Therapeutics, Concord, USA (GRID:grid.419517.f)
8 University of California San Francisco, Department of Microbiology and Immunology, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811)
9 Kaleido Biosciences, Lexington, USA (GRID:grid.266102.1); Flagship Pioneering, Cambridge, USA (GRID:grid.510906.b) (ISNI:0000 0004 6487 6319)
10 Kaleido Biosciences, Lexington, USA (GRID:grid.510906.b); Exo Therapeutics, Watertown, USA (GRID:grid.510906.b)
11 Kaleido Biosciences, Lexington, USA (GRID:grid.510906.b)