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

• DOI: 10.1038/s41467-020-18928-1
• Publication Date: 2020-10-09T10:02:37Z
• Authors: 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; David Berry
• Keywords: 0301 basic medicine; MUCIN; Cell Separation; Spectrum Analysis, Raman; Microbial ecology; INFECTION; EPIDEMIOLOGY; Intestinal Mucosa; IN-VIVO; 301305 Medizinische Chemie; 106022 Mikrobiologie; 0303 health sciences; GUT MICROBIOTA; Q; Monosaccharides; Anti-Bacterial Agents; GENOME; 106022 Microbiology; Female; Pathogens; 570; Science; Bacterial Toxins; 610; Article; Acetylglucosamine; 03 medical and health sciences; Bacterial Proteins; Polysaccharides; Animals; SUPPRESSION; Clostridioides difficile; 301305 Medical chemistry; Gastric Mucins; 500; Deuterium; N-Acetylneuraminic Acid; Gastrointestinal Microbiome; Mice, Inbred C57BL; MICE; Clostridium Infections; RNA; Metagenome; Metagenomics; Microbiome; info:eu-repo/classification/ddc/500; GENERATION

AbstractMany 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.