In vivo manipulation of human gut Bacteroides fitness by abiotic oligosaccharides

Darryl A. Wesener; Zachary W. Beller; Megan F. Hill; Han Yuan; David B. Belanger; Cheryl Frankfater; Nicolas Terrapon; Bernard Henrissat; Dmitry A. Rodionov; Semen A. Leyn; Andrei Osterman; Johan E. T. van Hylckama Vlieg; Jeffrey I. Gordon

doi:10.1038/s41589-024-01763-6

In vivo manipulation of human gut Bacteroides fitness by abiotic oligosaccharides

Darryl A. Wesener^*, Zachary W. Beller, Megan F. Hill, Han Yuan, David B. Belanger, Cheryl Frankfater, Nicolas Terrapon, Bernard Henrissat, Dmitry A. Rodionov, Semen A. Leyn, Andrei Osterman, Johan E. T. van Hylckama Vlieg, Jeffrey I. Gordon^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

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.

Original language	English
Journal	Nature Chemical Biology
Number of pages	29
ISSN	1552-4450
DOIs	https://doi.org/10.1038/s41589-024-01763-6
Publication status	Accepted/In press - 2025

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Wesener, D. A., Beller, Z. W., Hill, M. F., Yuan, H., Belanger, D. B., Frankfater, C., Terrapon, N., Henrissat, B., Rodionov, D. A., Leyn, S. A., Osterman, A., van Hylckama Vlieg, J. E. T., & Gordon, J. I. (Accepted/In press). In vivo manipulation of human gut Bacteroides fitness by abiotic oligosaccharides. Nature Chemical Biology. https://doi.org/10.1038/s41589-024-01763-6

@article{529d38ff052e4cca987e091061c2832c,

title = "In vivo manipulation of human gut Bacteroides fitness by abiotic oligosaccharides",

abstract = "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.",

author = "Wesener, {Darryl A.} and Beller, {Zachary W.} and Hill, {Megan F.} and Han Yuan and Belanger, {David B.} and Cheryl Frankfater and Nicolas Terrapon and Bernard Henrissat and Rodionov, {Dmitry A.} and Leyn, {Semen A.} and Andrei Osterman and {van Hylckama Vlieg}, {Johan E. T.} and Gordon, {Jeffrey I.}",

year = "2025",

doi = "10.1038/s41589-024-01763-6",

language = "English",

journal = "Nature Chemical Biology",

issn = "1552-4450",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - In vivo manipulation of human gut Bacteroides fitness by abiotic oligosaccharides

AU - Wesener, Darryl A.

AU - Beller, Zachary W.

AU - Hill, Megan F.

AU - Yuan, Han

AU - Belanger, David B.

AU - Frankfater, Cheryl

AU - Terrapon, Nicolas

AU - Henrissat, Bernard

AU - Rodionov, Dmitry A.

AU - Leyn, Semen A.

AU - Osterman, Andrei

AU - van Hylckama Vlieg, Johan E. T.

AU - Gordon, Jeffrey I.

PY - 2025

Y1 - 2025

N2 - 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.

AB - 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.

U2 - 10.1038/s41589-024-01763-6

DO - 10.1038/s41589-024-01763-6

M3 - Journal article

C2 - 39443715

SN - 1552-4450

JO - Nature Chemical Biology

JF - Nature Chemical Biology

ER -

In vivo manipulation of human gut Bacteroides fitness by abiotic oligosaccharides

Abstract

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