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

Erika Coletto, George M. Savva, Dimitrios Latousakis, Matthew Pontifex, Emmanuelle H. Crost, Laura Vaux, Andrea Telatin, Kirk Bergstrom, David Vauzour, Nathalie Juge

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Abstract

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.
Original languageEnglish
Article number13982
JournalScientific Reports
Volume13
DOIs
Publication statusPublished - 26 Aug 2023

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