Browsing by Subject "MUCUS LAYERS"

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  • Reunanen, Justus; Kainulainen, Veera; Huuskonen, Laura; Ottman, Noora; Belzer, Clara; Huhtinen, Heikki; de Vos, Willem M.; Satokari, Reetta (2015)
    Akkermansia muciniphila is a Gram-negative mucin-degrading bacterium that resides in the gastrointestinal tracts of humans and animals. A. muciniphila has been linked with intestinal health and improved metabolic status in obese and type 2 diabetic subjects. Specifically, A. muciniphila has been shown to reduce high-fat-diet-induced endotoxemia, which develops as a result of an impaired gut barrier. Despite the accumulating evidence of the health-promoting effects of A. muciniphila, the mechanisms of interaction of the bacterium with the host have received little attention. In this study, we used several in vitro models to investigate the adhesion of A. muciniphila to the intestinal epithelium and its interaction with the host mucosa. We found that A. muciniphila adheres strongly to the Caco-2 and HT-29 human colonic cell lines but not to human colonic mucus. In addition, A. muciniphila showed binding to the extracellular matrix protein laminin but not to collagen I or IV, fibronectin, or fetuin. Importantly, A. muciniphila improved enterocyte monolayer integrity, as shown by a significant increase in the transepithelial electrical resistance (TER) of cocultures of Caco-2 cells with the bacterium. Further, A. muciniphila induced interleukin 8 (IL-8) production by enterocytes at cell concentrations 100-fold higher than those for Escherichia coli, suggesting a very low level of proinflammatory activity in the epithelium. In conclusion, our results demonstrate that A. muciniphila adheres to the intestinal epithelium and strengthens enterocyte monolayer integrity in vitro, suggesting an ability to fortify an impaired gut barrier. These results support earlier associative in vivo studies and provide insights into the interaction of A. muciniphila with the host.
  • Geerlings, Sharon Y.; Kostopoulos, Ioannis; de Vos, Willem M.; Belzer, Clara (2018)
    Akkermansia muciniphila is a mucin-degrading bacterium of the phylum Verrucomicrobia. Its abundance in the human intestinal tract is inversely correlated to several disease states. A. muciniphila resides in the mucus layer of the large intestine, where it is involved in maintaining intestinal integrity. We explore the presence of Akkermansia-like spp. based on its 16S rRNA sequence and metagenomic signatures in the human body so as to understand its colonization pattern in time and space. A. muciniphila signatures were detected in colonic samples as early as a few weeks after birth and likely could be maintained throughout life. The sites where Akkermansia-like sequences (including Verrucomicrobia phylum and/or Akkermansia spp. sequences found in the literature) were detected apart from the colon included human milk, the oral cavity, the pancreas, the biliary system, the small intestine, and the appendix. The function of Akkermansia-like spp. in these sites may differ from that in the mucosal layer of the colon. A. muciniphila present in the appendix or in human milk could play a role in the re-colonization of the colon or breast-fed infants, respectively. In conclusion, even though A. muciniphila is most abundantly present in the colon, the presence of Akkermansia-like spp. along the digestive tract indicates that this bacterium might have more functions than those currently known.
  • Tytgat, Hanne L. P.; Nobrega, Franklin L.; van der Oost, John; de Vos, Willem M. (2019)
    Bacterial communities are known to impact human health and disease. Mixed species biofilms, mostly pathogenic in nature, have been observed in dental and gastric infections as well as in intestinal diseases, chronic gut wounds and colon cancer. Apart from the appendix, the presence of thick polymicrobial biofilms in the healthy gut mucosa is still debated. Polymicrobial biofilms containing potential pathogens appear to be an early-warning signal of developing disease and can be regarded as a tipping point between a healthy and a diseased state of the gut mucosa. Key biofilm-forming pathogens and associated molecules hold promise as biomarkers. Criteria to distinguish microcolonies from biofilms are crucial to provide clarity when reporting biofilm-related phenomena in health and disease in the gut.
  • Tailford, Louise E.; Owen, C. David; Walshaw, John; Crost, Emmanuelle H.; Hardy-Goddard, Jemma; Le Gall, Gwenaelle; de Vos, Willem M.; Taylor, Garry L.; Juge, Nathalie (2015)
    The gastrointestinal mucus layer is colonized by a dense community of microbes catabolizing dietary and host carbohydrates during their expansion in the gut. Alterations in mucosal carbohydrate availability impact on the composition of microbial species. Ruminococcus gnavus is a commensal anaerobe present in the gastrointestinal tract of > 90% of humans and overrepresented in inflammatory bowel diseases (IBD). Using a combination of genomics, enzymology and crystallography, we show that the mucin-degrader R. gnavus ATCC 29149 strain produces an intramolecular trans-sialidase (IT-sialidase) that cleaves off terminal alpha 2-3-linked sialic acid from glycoproteins, releasing 2,7-anhydro-Neu5Ac instead of sialic acid. Evidence of IT-sialidases in human metagenomes indicates that this enzyme occurs in healthy subjects but is more prevalent in IBD metagenomes. Our results uncover a previously unrecognized enzymatic activity in the gut microbiota, which may contribute to the adaptation of intestinal bacteria to the mucosal environment in health and disease.
  • Hugenholtz, Floor; de Vos, Willem M. (2018)
    Since the early days of the intestinal microbiota research, mouse models have been used frequently to study the interaction of microbes with their host. However, to translate the knowledge gained from mouse studies to a human situation, the major spatio-temporal similarities and differences between intestinal microbiota in mice and humans need to be considered. This is done here with specific attention for the comparative physiology of the intestinal tract, the effect of dietary patterns and differences in genetics. Detailed phylogenetic and metagenomic analysis showed that while many common genera are found in the human and murine intestine, these differ strongly in abundance and in total only 4% of the bacterial genes are found to share considerable identity. Moreover, a large variety of murine strains is available yet most of the microbiota research is performed in wild-type, inbred strains and their transgenic derivatives. It has become increasingly clear that the providers, rearing facilities and the genetic background of these mice have a significant impact on the microbial composition and this is illustrated with recent experimental data. This may affect the reproducibility of mouse microbiota studies and their conclusions. Hence, future studies should take these into account to truly show the effect of diet, genotype or environmental factors on the microbial composition.
  • Tytgat, Hanne L. P.; de Vos, Willem M. (2016)
    Tremendous progress has been made on mapping the mainly bacterial members of the human intestinal microbiota. Knowledge on what is out there, or rather what is inside, needs to be complemented with insight on how these bacteria interact with their biotic environment. Bacterial glycoconjugates, that is, the collection of all glycan-modified molecules, are ideal modulators of such interactions. Their enormous versatility and diversity results in a species-specific glycan barcode, providing a range of ligands for host interaction. Recent reports on the functional importance of glycosylation of important bacterial ligands in beneficial and pathogenic species underpin this. Glycoconjugates, and glycoproteins in particular, are an underappreciated, potentially crucial, factor in understanding bacteria-host interactions of old friends and foes.