Bacteria-associated VB12 regulates neonatal ileal epithelium homeostasis

项目摘要/摘要 阿尔茨海默病和相关痴呆(ADRD)严重削弱宿主记忆，宿主功能 才能。因此，目前还没有有效的治疗策略可用于临床环境。 研究阐明了微量营养素(例如，维生素、氨基酸)在缓解 神经退行性变，导致宿主认知功能下降的改善。因此，阐明微量营养素- 相关方法可能会减轻主机内存损失。维生素B12(VB12)是维持人体健康的关键因素。 肠上皮平衡和功能微生物组生理学对抗诱导的中毒性炎症。 相比之下，VB12缺乏会使致病性炎症持续存在，最终导致肠道破坏。 分子动态平衡。此外，我们发现VB12在功能上调节树突状细胞、小胶质细胞和大脑 脂质体，所有这些都可以控制诱导的神经炎症。进一步挖掘VB12中S的功能能力 维持脑树以潜在地控制对侧病变的病理，这一管理的目标 补充研究建议是进一步阐明VB12-参与大脑功能的硬连接 Tregs可以限制小胶质细胞的不受控制的激活，这可能与tautation依赖的记忆下降有关。 我们的假设是，VB12紧密维持大脑Treg的稳态，以限制与直立性疾病相关的 神经炎症，导致宿主记忆力丧失明显改善。具体目标是：1. 研究VB12在维持功能性大脑皮层功能中的相关性，以限制相互作用的病理，和2。 阐明树突状细胞对小胶质细胞的调节，可能有助于改善记忆 拒绝。这项行政补充研究提案的预测结果将是第一次深入 VB12通过功能树调节脑内环境平衡潜在降低宿主的研究报告 记忆力衰退。

Project Summary/Abstract Alzheimer's disease and related dementias (ADRD) critically debilitate the host memory, and host functional ability. Accordingly, no efficacious therapeutic strategies are currently available to translate into clinical settings. Studies illuminate the pivotal role of micronutrients (e.g., vitamins, amino acids) in alleviating induced neurodegeneration, resulting in the improvement of host cognitive decline. Thus, elucidating micronutrient- dependent approaches may mitigate host memory loss. Vitamin B12 (VB12) is a crucial factor that sustains the intestinal epithelium equilibrium, and functional microbiome physiology against induced toxic inflammation. Contrastingly, VB12-deficiency perpetuates pathogenic inflammation, culminating in the disruption of intestinal molecular homeostasis. Additionally, we show that VB12 functionally regulates Tregs, microglia, and the cerebral lipidomes, all of which may control induced neuroinflammation. To further delve into VB12’s ability in functionally sustaining cerebral Tregs to potentially control tauopathy pathology, the objective of this administrative supplement research proposal is to further elucidate VB12-involvement in hardwiring the functions of cerebral Tregs to limit uncontrolled activation of microglia, potentially implicated in tauopathy-dependent memory decline. Our hypothesis is that VB12 tightly maintains the cerebral Treg homeostasis to limit tauopathy-associated neuroinflammation, leading to significant improvement of the host memory loss. The specific aims are: 1. Investigate the relevance of VB12 in maintaining functional cerebral Tregs to limit tauopathy pathology, and 2. Elucidate the regulation of microglia cells by Tregs, potentially contributing to the improvement of memory decline. The predicted outcomes of this administrative supplement research proposal will be the first in-depth report on VB12 in tonically regulating brain homeostasis through functional Tregs to potentially reduce host memory decline.