Ruminococcus torquesis a keystone degrader of intestinal mucin glycoprotein, releasing oligosaccharides used byBacteroides thetaiotaomicron

Abstract

AbstractSymbiotic interactions between humans and our communities of resident gut microbes (microbiota) play many roles in health and disease. Some gut bacteria utilize mucus as a nutrient source and can under certain conditions damage the protective barrier it forms, increasing disease susceptibility. We investigated howRuminococcus torques—a known mucin-degrader that remains poorly studied despite its implication in inflammatory bowel diseases (IBDs)— degrades mucin glycoproteins or their componentO-linked glycans to understand its effects on the availability of mucin-derived nutrients for other bacteria. We found thatR. torquesutilizes both mucin glycoproteins and released oligosaccharides from gastric and colonic mucins, degrading these substrates with a panoply of mostly constitutively expressed, secreted enzymes. Investigation of mucin oligosaccharide degradation byR. torquesrevealed strong fucosidase, sialidase and β1,4-galactosidase activities. There was a lack of detectable sulfatase and weak β1,3-galactosidase degradation, resulting in accumulation of glycans containing these structures on mucin polypeptides. While the Gram-negative symbiont,Bacteroides thetaiotaomicrongrows poorly on mucin glycoproteins, we demonstrate a clear ability ofR. torquesto liberate products from mucins, making them accessible toB. thetaiotaomicron. This work underscores the diversity of mucin-degrading mechanisms in different bacterial species and the probability that some species are contingent on others for the ability to more fully access mucin-derived nutrients. The ability ofR. torquesto directly degrade a variety of mucin and mucin glycan structures and unlock released glycans for other species suggests that it is a keystone mucin degrader, which may contribute to its association with IBD.ImportanceAn important facet of maintaining healthy symbiosis between host and intestinal microbes is the mucus layer, the first defense protecting the epithelium from lumenal bacteria. Some gut bacteria degrade different components of intestinal mucins, but detailed mechanisms used by different species are still emerging. It is imperative to understand these mechanisms as they likely dictate interspecies interactions and may illuminate particular species associated with bacterial mucus destruction and subsequent disease susceptibility.Ruminococcus torquesis positively associated with IBD in multiple studies. We identified mucin glycan-degrading enzymes inR. torquesand found that it shares mucin degradation products with another gut bacterium implicated in IBD,Bacteroides thetaiotaomicron. Our findings underscore the importance of understanding the mucin degradation mechanisms of different gut bacteria and their consequences on interspecies interactions, which may identify keystone bacteria that disproportionately contribute to defects in mucus protection and could therefore be targets to prevent or treat IBD.