Similar Datasets
Project description: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.
2020-10-28 | GSE133174 | GEO
Project description: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.
2020-10-28 | GSE133256 | GEO
Project description:Ascending colon-derived mucin-type O-glycans form key mucus layers encapsulating microbiota in the colon
| PRJNA550524 | ENA
Project description:Ascending colon-derived mucin-type O-glycans form key mucus layers encapsulating microbiota in the colon (RNA-seq)
| PRJNA550137 | ENA
Project description:Ascending colon-derived mucin-type O-glycans form key mucus layers encapsulating microbiota in the colon (16S rNA-seq)
| PRJNA550526 | ENA
Project description:We normally live in symbiosis with approximately 10(13) bacteria present in the colon. Among the several mechanisms maintaining the bacteria/host balance, there is limited understanding of the structure, function, and properties of intestinal mucus. We now demonstrate that the mouse colonic mucus consists of two layers extending 150 mum above the epithelial cells. Proteomics revealed that both of these layers have similar protein composition, with the large gel-forming mucin Muc2 as the major structural component. The inner layer is densely packed, firmly attached to the epithelium, and devoid of bacteria. In contrast, the outer layer is movable, has an expanded volume due to proteolytic cleavages of the Muc2 mucin, and is colonized by bacteria. Muc2(-/-) mice have bacteria in direct contact with the epithelial cells and far down in the crypts, explaining the inflammation and cancer development observed in these animals. These findings show that the Muc2 mucin can build a mucus barrier that separates bacteria from the colon epithelia and suggest that defects in this mucus can cause colon inflammation.
| S-EPMC2567493 | biostudies-literature
Project description:The fate of macromolecules of biological or pharmacological interest that enter the mucus barrier is a current field of investigation. Studies of the interaction between the main constituent of mucus, mucins, and molecules involved in topical transmucoidal drug or gene delivery is a prerequisite for nanomedicine design. We studied the interaction of mucin with the bio-inspired arginine-derived amphoteric polymer d,l-ARGO7 by applying complementary techniques. Small angle X-ray scattering in bulk unveiled the formation of hundreds of nanometer-sized clusters, phase separated from the mucin mesh. Quartz microbalance with dissipation and neutron reflectometry measurements on thin mucin layers deposited on silica supports highlighted the occurrence of polymer interaction with mucin on the molecular scale. Rinsing procedures on both experimental set ups showed that interaction induces alteration of the deposited hydrogel. We succeeded in building up a new significant model for epithelial tissues covered by mucus, obtaining the deposition of a mucin layer 20 Å thick on the top of a glycolipid enriched phospholipid single membrane, suitable to be investigated by neutron reflectometry. The model is applicable to unveil the cross structural details of mucus-covered epithelia in interaction with macromolecules within the Å discreteness.
| S-EPMC6695901 | biostudies-literature
Project description:Microbiota-accessible carbohydrates (MACs) are powerful modulators of microbiota composition and function. These substrates are often derived from diet, such as complex polysaccharides from plants or human milk oligosaccharides (HMOs) during breastfeeding. Host-derived mucus glycans on gut-secreted mucin proteins serve as a continuous endogenous source of MACs for resident microbes; here we investigate the potential role of purified, orally administered mucus glycans in maintaining a healthy microbial community. In this study, we liberated and purified O-linked glycans from porcine gastric mucin and assessed their efficacy in shaping the recovery of a perturbed microbiota in a mouse model. We found that porcine mucin glycans (PMGs) and HMOs enrich for taxonomically similar resident microbes. We demonstrate that PMGs aid recovery of the microbiota after antibiotic treatment, suppress Clostridium difficile abundance, delay the onset of diet-induced obesity, and increase the relative abundance of resident Akkermansia muciniphila. In silico analysis revealed that genes associated with mucus utilization are abundant and diverse in prevalent gut commensals and rare in enteric pathogens, consistent with these glycan-degrading capabilities being selected for during host development and throughout the evolution of the host-microbe relationship. Importantly, we identify mucus glycans as a novel class of prebiotic compounds that can be used to mitigate perturbations to the microbiota and provide benefits to host physiology.
| S-EPMC8027378 | biostudies-literature
Project description:The glycoproteins of tumour cells are often abnormal, both in structure and in quantity. In particular, the mucin-type O-glycans have several cancer-associated structures, including the T and Tn antigens, and certain Lewis antigens. These structural changes can alter the function of the cell, and its antigenic and adhesive properties, as well as its potential to invade and metastasize. Cancer-associated mucin antigens can be exploited in diagnosis and prognosis, and in the development of cancer vaccines. The activities and Golgi localization of glycosyltransferases are the basis for the glycodynamics of cancer cells, and determine the ranges and amounts of specific O-glycans produced. This review focuses on the glycosyltransferases of colon and breast cancer cells that determine the pathways of mucin-type O-glycosylation, and the proposed functional and pathological consequences of altered O-glycans.
| S-EPMC1479595 | biostudies-literature
Project description:Complex microbial populations are organized in relation to their environment. In the intestine, the inner lining (mucosa) is a potential focal point for such organization. The proximal murine colon contains mucosal folds that are known to be associated with morphologically distinct microbes. To identify these microbes, we used the technique of laser capture microdissection (LCM) to sample microbes associated with these folds (interfold region) and within the central lumen (digesta region). Using 16S rRNA gene tag pyrosequencing, we found that microbes in the interfold region were highly enriched for the phylum Firmicutes and, more specifically, for the families Lachnospiraceae and Ruminococcaceae. Other families such as Bacteroidaceae, Enterococcaceae and Lactobacillaceae were all enriched in the digesta region. This high-resolution system to capture and examine spatial organization of intestinal microbes should facilitate microbial analysis in other mouse models, furthering our understanding of host-microbial interactions.
| S-EPMC3105732 | biostudies-literature