Role of mucin glycosylation in the gut microbiota-brain axis of core 3 O-glycan deficient mice

Coletto, Erika, Savva, George M., Latousakis, Dimitrios, Pontifex, Matthew ORCID:, Crost, Emmanuelle H., Vaux, Laura, Telatin, Andrea, Bergstrom, Kirk, Vauzour, David ORCID: and Juge, Nathalie (2023) Role of mucin glycosylation in the gut microbiota-brain axis of core 3 O-glycan deficient mice. Scientific Reports, 13. ISSN 2045-2322

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Alterations in intestinal mucin glycosylation have been associated with increased intestinal permeability and sensitivity to inflammation and infection. Here, we used mice lacking core 3-derived O-glycans (C3GnT−/−) to investigate the effect of impaired mucin glycosylation in the gut-brain axis. C3GnT−/− mice showed altered microbial metabolites in the caecum associated with brain function such as dimethylglycine and N-acetyl-L-tyrosine profiles as compared to C3GnT+/+ littermates. In the brain, polysialylated-neural cell adhesion molecule (PSA-NCAM)-positive granule cells showed an aberrant phenotype in the dentate gyrus of C3GnT−/− mice. This was accompanied by a trend towards decreased expression levels of PSA as well as ZO-1 and occludin as compared to C3GnT+/+. Behavioural studies showed a decrease in the recognition memory of C3GnT−/− mice as compared to C3GnT+/+ mice. Combined, these results support the role of mucin O-glycosylation in the gut in potentially influencing brain function which may be facilitated by the passage of microbial metabolites through an impaired gut barrier.

Item Type: Article
Additional Information: Data availability: The authors confirm that the data supporting the findings of this study are available within the article and its Supplementary Materials. The raw reads produced for the metabarcoding analysis of this project are available at the EBI ENA, under Project Accession ID PRJEB57587 and study ID ERP142578. The metabolomics data will be made available on demand to the corresponding author. Funding information: The authors gratefully acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC); this research was funded by the BBSRC Institute Strategic Programme Grant Gut Microbes and Health BB/R012490/1 and its constituent projects BBS/E/F/000PR10353 (Theme 1, Determinants of microbe-host responses in the gut across life) and EC held a BBSRC Norwich Research Park Doctoral Training Grant BB/M011216/1. GS and AT were supported by the BBSRC Core Capability Grant BB/CCG1860/1. The authors acknowledge Mohammad K. Hajihosseini for access to the vibratome and Herbert Hildebrandt for the antibodies and reagents to detect PSA-NCAM by western blot analysis. The bioinformatics analyses have been performed using the computing capacity provided by MRC CLIMB BIG DATA Grant MR/T030062/1.
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Medicine and Health Sciences > School of Health Sciences
Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine
Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging
Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health
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Depositing User: LivePure Connector
Date Deposited: 30 Aug 2023 14:30
Last Modified: 05 Dec 2023 02:32
DOI: 10.1038/s41598-023-40497-8


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