Proximal colon–derived O-glycosylated mucus encapsulates and modulates the microbiota

Abstract

Colon mucus segregates the intestinal microbiota from host tissues, but how it organizes to function throughout the colon is unclear. In mice, we found that colon mucus consists of two distinct O-glycosylated entities of Muc2: a major form produced by the proximal colon, which encapsulates the fecal material including the microbiota, and a minor form derived from the distal colon, which adheres to the major form. The microbiota directs its own encapsulation by inducing Muc2 production from proximal colon goblet cells. In turn, O-glycans on proximal colon–derived Muc2 modulate the structure and function of the microbiota as well as transcription in the colon mucosa. Our work shows how proximal colon control of mucin production is an important element in the regulation of host-microbiota symbiosis.

PET/CT targeted tissue sampling reveals virus specific dIgA can alter the distribution and localization of HIV after rectal exposure

“…between the descending colon and the rectum. 32 . Alternatively, the dIgA stimulated trafficking to the mesenteric lymph nodes that drain the descending colon in animals given dIgA would move penetrating virions deeper into the tissue and beyond our analysis of the epithelial barriers.…”

Microbe–Mucus Interface in the Pathogenesis of Colorectal Cancer

“…This relationship between the microbiota and mucus is very intricate. A recent publication by Bergstrom et al has added another functional aspect to mucus, demonstrating that proximally derived O-glycosylated mucus encapsulates fecal material and the microbiota to modulate microbiota structure and function, as well as transcription in the colon mucosa [28]. Interestingly, the microbiota directs its own encapsulation by inducing Muc2 production from proximal colon goblet cells [28].…”

“…A recent publication by Bergstrom et al has added another functional aspect to mucus, demonstrating that proximally derived O-glycosylated mucus encapsulates fecal material and the microbiota to modulate microbiota structure and function, as well as transcription in the colon mucosa [28]. Interestingly, the microbiota directs its own encapsulation by inducing Muc2 production from proximal colon goblet cells [28]. This work has also introduced a major revision to the current mucus system model of locally produced mucus through the identification of two distinct O-glycosylated entities of MUC2: a major form produced by the proximal colon that encapsulates and shapes the microbiota and a minor form derived from the distal colon that adheres to the major form [28].…”

“…Interestingly, the microbiota directs its own encapsulation by inducing Muc2 production from proximal colon goblet cells [28]. This work has also introduced a major revision to the current mucus system model of locally produced mucus through the identification of two distinct O-glycosylated entities of MUC2: a major form produced by the proximal colon that encapsulates and shapes the microbiota and a minor form derived from the distal colon that adheres to the major form [28]. Its high water content renders the mucus layer as a lubricant that protects against dehydration and mechanical stress [29].…”

“…In light of the bidirectional interaction of microbes and mucus, targeting the gut microbiota to increase the mucosal barrier forms a major research goal. Furthermore, studies such as the recent work by Bergstrom et al investigating fecal-associated mucus [28] provide new insights into microbiota metabolism and composition and may lead to noninvasive strategies such as fecal mucus screening for disease diagnosis. Experimental efforts need to address not only how individual bacteria interact with and utilize specific mucin glycans, but also how this affects mucus expression, glycosylation, and secretion.…”