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Davey, L.

Publications and source records attributed to Davey, L..

3 recordsLinked to original sources

Rapid early life colonization of the intestinal tract by Akkermansia muciniphila after voluntary feeding

BackgroundNon-invasive methods to colonize intact gut microbiota populations with specific bacterial species are useful for experimental studies that advance our understanding of this commensal microbial population in health and disease. Within the gut microbiota, the anaerobic muciniphile Akkermansia muciniphila has many established health benefits. We report the development of a new voluntary feeding protocol for non-invasive administration of bacteria into the intestine and use it to characterize the early life colonization of the intestinal tract by A. muciniphila. ResultsMice were voluntarily fed a human strain of A. muciniphila (MucT/BAA-835) in the week after weaning, whereupon they consistently and rapidly ingested the bacterium. At this developmental period, conventionally housed mice were rapidly colonized by human A. muciniphila that persisted until at least 8 weeks of age. In mice that contained a dysbiotic gut microbiota that lack endogenous A. muciniphila, voluntary feeding with human A. muciniphila similarly led to rapid and stable colonization. Colonization was similar in female and male mice. Also, in conventionally housed mice there was incomplete colonization of the intestinal tract with endogenous A. muciniphila between 3 - 4 weeks of age, which enabled its competitive exclusion by human A. muciniphila that was orally delivered. ConclusionsThese findings establish a new and non-invasive approach for colonizing the intestinal tract with commensal microbes that provides information on the early life colonization of the gut microbiota with A. muciniphila.

microbiology↗

The role of Akkermansia muciniphila sulfatases in colonic mucinutilisation

Akkermansia muciniphila, an obligate mucin degrader, is a major member of the human colonic microbiota and has been associated positive health outcomes. Mucins are complex glycoproteins that contain heavily sulfated O-glycans and form the protective colonic mucus layer. Bacterial carbohydrate sulfatases are required to metabolise these heavily sulfated mucin glycans and excessive bacterial foraging has been associated with several diseases. Sulfatases have been linked with inflammatory bowel disease, making these microbiota enzymes potential drug targets. A. muciniphila expresses carbohydrate sulfatases that can act on colonic mucins yet their roles in its metabolism remain opaque. Our data reveal that A. muciniphila requires glycopeptides/protein forms of colonic mucin for metabolism and its sulfatases have unique adaptations compared to Bacteroides species. Localisation studies reveal that desulfation of N-acetyl-D-glucosamine, but not D-galactose, is exclusively periplasmic. A cell surface sulfatase has a novel carbohydrate binding module that binds to colonic mucin. This paints a contrasting picture of sulfated mucin metabolism by Akkermansia muciniphila versus Bacteroides species. These data will be important for understanding the contexts for Akkermansia muciniphilas positive health correlations.

biochemistry↗

Pitfalls in re-analysis of observational omics studies: a post-mortem of the human pathology atlas.

Uhlen et al. (Reports, 18 august 2017) published an open-access resource with cancer-specific marker genes that are prognostic for patient survival in seventeen different types of cancer. However, their data analysis workflow is prone to the accumulation of false positives. A more reliable workflow with flexible Cox proportional hazards models employed on the same data highlights three distinct problems with such large-scale, publicly available omics datasets from observational studies today: (i) re-analysis results can not necessarily be taken forward by others, highlighting a need to cross-check important analyses with high impact outcomes; (ii) current methods are not necessarily optimal for the re-analysis of such data, indicating an urgent need to develop more suitable methods; and (iii) the limited availability of potential confounders in public metadata renders it very difficult (if not impossible) to adequately prioritize clinically relevant genes, which should prompt an in-depth discussion on how such information could be made more readily available while respecting privacy and ethics concerns.

bioinformatics↗