Ascending colon-derived mucin-type O-glycans form key mucus layers encapsulating microbiota in the colon (RNA-seq)

The colon contains a dense metabolically potent microbiota. The colonic O-glycan-rich mucus has been recognized as a key barrier to prevent microbial intrusion, but how this system forms and functions remains unclear. Here, we discovered that the colon mucus is mainly forged by microbiota-dependent secretion of O-glycosylated Muc2 by goblet cells in the ascending colon, where it seamlessly encapsulates the fecal materials including the microbiota. Deletion of O-glycans in the ascending colon impaired the segregating function of the mucous coating, leading to altered structure and metabolic output of the microbiota, and transcriptional homeostasis of the entire host mucosa. These findings represent a paradigm change of the prevailing model of the colon mucus system and provides new insights into host and microbiota symbiosis. Overall design: RNA seq was performed on mouse colon tissue derived from the ascending and descending colon. Global gene expression profiles were compared between 3 Groups of Healthy Control and O-glycan mutant littermates that were all colonized with the same microbiota