Bacteria-associated VB12 regulates neonatal ileal epithelium homeostasis

University Of Texas Hlth Science Center, San Antonio TX

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Abstract

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.