In vivo manipulation of human gut Bacteroides fitness by abiotic oligosaccharides
Synthetic glycans (SGs) containing glycosidic linkages and structures not identified in nature offer a means for deliberately altering microbial community properties. Here pools of SG oligosaccharides were generated via polymerization of monosaccharides and screened for their ability to increase saccharolytic Bacteroides in ex vivo cultures of human fecal samples. A lead SG preparation was orally administered to gnotobiotic mice harboring a consortium of 56 cultured, phylogenetically diverse human gut bacteria and fed a Western diet. The abundances of 3 of 15 Bacteroides strains increased, most prominently B. intestinalis. Underlying mechanisms were characterized by analyzing in vivo expression of the carbohydrate utilization machinery, using retrievable microscopic paramagnetic particles with bound SG oligosaccharides and assaying SG degradation by individual purified B. intestinalis glycoside hydrolases. The results reveal that SGs can selectively co-opt carbohydrate utilization machinery in different human gut Bacteroides and demonstrate a means for identifying artificial carbohydrate structures for targeted bacterial manipulation.
Authors
- Johan E. T. van Hylckama Vlieg (ORCID: https://orcid.org/0000-0001-6656-8668)
- Semen A. Leyn (ORCID: https://orcid.org/0000-0002-9886-9120)
- Andrei L. Osterman (ORCID: https://orcid.org/0000-0002-3810-9824)
- Megan Hill (ORCID: https://orcid.org/0000-0001-6128-6338)
- Zachary Beller (ORCID: https://orcid.org/0000-0003-3965-9147)
- Dmitry A. Rodionov (ORCID: https://orcid.org/0000-0002-0939-390X)
- Nicolas Terrapon (ORCID: https://orcid.org/0000-0002-3693-6017)
- Cheryl Frankfater (ORCID: https://orcid.org/0000-0002-6867-8518)
- Bernard Henrissat (ORCID: https://orcid.org/0000-0002-3434-8588)
- Darryl A. Wesener (ORCID: https://orcid.org/0000-0002-8132-7018)
- Jeffrey I. Gordon (ORCID: https://orcid.org/0000-0001-8304-3548)
- Han Yuan (ORCID: https://orcid.org/0000-0002-2674-6068)
- David Belanger (ORCID: https://orcid.org/0000-0001-9673-1630)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Washington University in St. Louis (US)
- Aix-Marseille Université (FR)
- Discovery Institute (US)
- Architecture et Fonction des Macromolécules Biologiques (FR)
- The Ohio State University (US)
- Technical University of Denmark (DK)
Publication Details
- Journal
- Nature Chemical Biology
- Published
- 2024-10-23
- DOI
- https://doi.org/10.1038/s41589-024-01763-6
- Citations
- 1
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.23
Funders
- Damon Runyon Cancer Research Foundation
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases
- Center for Scientific Review
- Office of Extramural Research, National Institutes of Health
- National Center for Complementary and Integrative Health