Oral Administration of Lactobacillus sakei CVL-001 Improves Recovery from Dextran Sulfate Sodium-Induced Colitis in Mice by Microbiota Modulation.

Inflammatory bowel disease (IBD) is an intestinal chronic inflammatory disease, and its incidence is steadily increasing. IBD is closely related to the intestinal microbiota, and probiotics are known to be a potential therapeutic agent for IBD. In our study, we evaluated the protective effect of Lactobacillus sakei CVL-001, isolated from Baechu kimchi, on dextran sulfated sodium (DSS)-induced colitis in mice. The oral administration of L. sakei CVL-001 according to the experimental schedule alleviated weight loss and disease activity in the mice with colitis. Furthermore, the length and histopathology of the colon improved. The expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß genes decreased in the colons of mice that were administered L. sakei CVL-001, whereas that of IL-10 increased. The expressions of genes coding for E-cadherin, claudin3, occludin, and mucin were also restored. In co-housed conditions, L. sakei CVL-001 administration did not improve disease activity, colon length, and histopathology. Microbiota analysis revealed that L. sakei CVL-001 administration increased the abundance of microbiota and altered Firmicutes/Bacteroidetes ratio, and decreased Proteobacteria. In conclusion, L. sakei CVL-001 administration protects mice from DSS-induced colitis by regulating immune response and intestinal integrity via gut microbiota modulation.

Memory and synaptic plasticity are impaired by dysregulated hippocampal O-GlcNAcylation.

O-GlcNAcylated proteins are abundant in the brain and are associated with neuronal functions and neurodegenerative diseases. Although several studies have reported the effects of aberrant regulation of O-GlcNAcylation on brain function, the roles of O-GlcNAcylation in synaptic function remain unclear. To understand the effect of aberrant O-GlcNAcylation on the brain, we used Oga+/- mice which have an increased level of O-GlcNAcylation, and found that Oga+/- mice exhibited impaired spatial learning and memory. Consistent with this result, Oga+/- mice showed a defect in hippocampal synaptic plasticity. Oga heterozygosity causes impairment of both long-term potentiation and long-term depression due to dysregulation of AMPA receptor phosphorylation. These results demonstrate a role for hyper-O-GlcNAcylation in learning and memory.