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

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.