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Rational design of a microbial consortium of mucosal sugar utilizers reduces Clostridiodes difficile colonization

Fátima C. Pereira, Kenneth Wasmund, Iva Cobankovic, Nico Jehmlich, Craig W. Herbold, Kang Soo Lee, Barbara Sziranyi, Cornelia Vesely, Thomas Decker, Roman Stocker, Benedikt Warth, Martin von Bergen, Michael Wagner and David Berry ()
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Fátima C. Pereira: University of Vienna, Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science
Kenneth Wasmund: University of Vienna, Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science
Iva Cobankovic: University of Vienna, Faculty of Chemistry, Department of Food Chemistry and Toxicology
Nico Jehmlich: Helmholtz-Centre for Environmental Research - UFZ, Department of Molecular Systems Biology
Craig W. Herbold: University of Vienna, Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science
Kang Soo Lee: Ralph M. Parsons Laboratory for Environmental Science and Engineering, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology
Barbara Sziranyi: University of Vienna, Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science
Cornelia Vesely: Medical University of Vienna, Center for Anatomy and Cell Biology, Division of Cell and Developmental Biology
Thomas Decker: Max F. Perutz Laboratories, Department of Microbiology, Immunobiology and Genetics, University of Vienna
Roman Stocker: Ralph M. Parsons Laboratory for Environmental Science and Engineering, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology
Benedikt Warth: University of Vienna, Faculty of Chemistry, Department of Food Chemistry and Toxicology
Martin von Bergen: Helmholtz-Centre for Environmental Research - UFZ, Department of Molecular Systems Biology
Michael Wagner: University of Vienna, Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science
David Berry: University of Vienna, Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Many intestinal pathogens, including Clostridioides difficile, use mucus-derived sugars as crucial nutrients in the gut. Commensals that compete with pathogens for such nutrients are therefore ecological gatekeepers in healthy guts, and are attractive candidates for therapeutic interventions. Nevertheless, there is a poor understanding of which commensals use mucin-derived sugars in situ as well as their potential to impede pathogen colonization. Here, we identify mouse gut commensals that utilize mucus-derived monosaccharides within complex communities using single-cell stable isotope probing, Raman-activated cell sorting and mini-metagenomics. Sequencing of cell-sorted fractions reveals members of the underexplored family Muribaculaceae as major mucin monosaccharide foragers, followed by members of Lachnospiraceae, Rikenellaceae, and Bacteroidaceae families. Using this information, we assembled a five-member consortium of sialic acid and N-acetylglucosamine utilizers that impedes C. difficile’s access to these mucosal sugars and impairs pathogen colonization in antibiotic-treated mice. Our findings underscore the value of targeted approaches to identify organisms utilizing key nutrients and to rationally design effective probiotic mixtures.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18928-1

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DOI: 10.1038/s41467-020-18928-1

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