Mucin-Degrading Microbes Release Monosaccharides That Chemoattract <i>Clostridioides difficile</i> and Facilitate Colonization of the Human Intestinal Mucus Layer

Abstract

It is widely accepted that the pathogen <i>Clostridioides difficile</i> exploits an intestinal environment with an altered microbiota, but the details of these microbe-microbe interactions are unclear. Adherence and colonization of mucus has been demonstrated for several enteric pathogens and it is possible that mucin-associated microbes may be working in concert with <i>C. difficile</i>. We showed that <i>C. difficile</i> ribotype-027 adheres to MUC2 glycans and using fecal bioreactors, we identified that <i>C. difficile</i> associates with several mucin-degrading microbes. <i>C. difficile</i> was found to chemotax toward intestinal mucus and its glycan components, demonstrating that <i>C. difficile</i> senses the mucus layer. Although <i>C. difficile</i> lacks the glycosyl hydrolases required to degrade mucin glycans, coculturing <i>C. difficile</i> with the mucin-degrading <i>Akkermansia muciniphila</i>, <i>Bacteroides thetaiotaomicron</i>, and <i>Ruminococcus torques</i> allowed <i>C. difficile</i> to grow in media that lacked glucose but contained purified MUC2. Collectively, these studies expand our knowledge on how intestinal microbes support <i>C. difficile</i>.