Rational design of a microbial consortium of mucosal sugar utilizers reduces Clostridiodes difficile colonization.
Fátima C PereiraKenneth WasmundIva CobankovicNico JehmlichCraig W HerboldKang Soo LeeBarbara SziranyiCornelia VeselyThomas DeckerRoman StockerBenedikt WarthMartin von BergenMichael WagnerDavid BerryPublished in: Nature communications (2020)
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.
Keyphrases
- single cell
- clostridium difficile
- rna seq
- gram negative
- heavy metals
- high throughput
- physical activity
- healthcare
- candida albicans
- human health
- risk assessment
- metabolic syndrome
- type diabetes
- antimicrobial resistance
- health information
- cancer therapy
- stem cells
- ulcerative colitis
- mesenchymal stem cells
- adipose tissue
- skeletal muscle
- cell surface