Gut Microbes and Health Institute Strategic Programme, Quadram Institute Bioscience, Norwich, NR4 7UQ, UK.
Norwich Medical School, Biomedical Research Centre, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
Sci Rep. 2023 Aug 26;13(1):13982. doi: 10.1038/s41598-023-40497-8.
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.
肠道粘蛋白糖基化的改变与肠道通透性的增加以及对炎症和感染的敏感性有关。在这里，我们使用缺乏核心 3 衍生 O-聚糖 (C3GnT) 的小鼠来研究肠道-大脑轴中粘蛋白糖基化受损的影响。与 C3GnT 同窝仔相比，C3GnT 小鼠的盲肠中存在与大脑功能相关的改变的微生物代谢物，如二甲氨基甘氨酸和 N-乙酰-L-酪氨酸谱。在大脑中，PSA-NCAM 阳性颗粒细胞在 C3GnT 小鼠的齿状回中表现出异常表型。与 C3GnT 相比，这伴随着 PSA 以及 ZO-1 和闭合蛋白表达水平的趋势下降。行为研究表明，与 C3GnT 相比，C3GnT 小鼠的识别记忆减少。综合这些结果支持粘蛋白 O-糖基化在肠道中可能通过受损的肠道屏障影响大脑功能的作用，这可能是通过微生物代谢物的通过来促进的。
