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Rational design of a microbial consortium of mucosal sugar utilizers reduces Clostridiodes difficile colonization
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Rational design of a microbial consortium of mucosal sugar utilizers reduces Clostridiodes difficile colonization
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Journal Article
Rational design of a microbial consortium of mucosal sugar utilizers reduces Clostridiodes difficile colonization
2020
Overview
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.
Here, the authors employ Raman-Activated Cell Sorting (RACS) and metagenomics to identify organisms that can forage on
O
-glycan monosaccharides in the mouse gut, which they use to construct a bacterial consortium able to reduce
Clostridioides difficile
colonization based on competition for mucosal sugars.
Publisher
Nature Publishing Group UK,Nature Portfolio
Subject
/ 45
/ 45/88
/ 49/22
/ 49/23
/ 82/58
/ Acetylglucosamine - metabolism
/ Animals
/ Bacterial Proteins - metabolism
/ Bacterial Toxins - metabolism
/ Clostridioides difficile - genetics
/ Clostridioides difficile - growth & development
/ Clostridioides difficile - pathogenicity
/ Clostridium Infections - microbiology
/ Female
/ Gastrointestinal Microbiome - physiology
/ Humanities and Social Sciences
/ Intestinal Mucosa - drug effects
/ Intestinal Mucosa - microbiology
/ Monosaccharides - metabolism
/ N-Acetylneuraminic Acid - metabolism
/ Polysaccharides - metabolism
/ Science
