Bacteria-associated VB12 regulates neonatal ileal epithelium homeostasis

细菌相关的 VB12 调节新生儿回肠上皮稳态

基本信息

批准号：
10712066
负责人：
Mansour M Zadeh
金额：
$ 38.51万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10712066
关键词：
Activities of Daily Living Administrative Supplement Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Amino Acids Antiinflammatory Effect Antioxidants Axon Bacteria Brain Calibration Cell Death Cell physiology Cells Cerebrum Cessation of life Clinical Cognitive Cognitive deficits Colorectal Cancer Complex Cytoplasm DNA Epithelial Cells Epithelium Equilibrium Genomics Glutamates Homeostasis Homocysteine Immune System Diseases Impaired cognition Inflammation Intestines Knowledge Language Disorders Megaloblastic Anemia Memory Memory Loss Methionine Methylation Methylmalonyl-CoA Mutase Microglia Micronutrients Microtubules Mitochondria Molecular Movement Mus Neonatal Nerve Degeneration Nervous System Physiology Neurodegenerative Disorders Neurofibrillary Tangles Neurons Outcome Pathogenicity Pathologic Pathology Physiology Process Property Regimen Regulation Regulatory T-Lymphocyte Reporting Research Research Proposals Risk Factors Role Shapes Signal Transduction Symptoms T-Lymphocyte Tauopathies Therapeutic Time Transcript Translating Traumatic Brain Injury Vitamin B 12 Vitamin B 12 Deficiency Vitamins amino acid metabolism cellular development cerebral atrophy cofactor design dietary epigenomics hyperphosphorylated tau improved insight intestinal epithelium lipidome metabolome methylmalonyl-coenzyme A microbiome microbiota micronutrient deficiency mild traumatic brain injury mouse model multiple omics myelination nervous system disorder neuroinflammation neuron loss neuropsychiatry neurotoxicity novel outcome prediction programs response succinyl-coenzyme A synaptic function tau Proteins transcriptome

项目摘要

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.

项目概要/摘要阿尔茨海默病和相关痴呆（ADRD）严重削弱宿主记忆和宿主功能因此，目前尚无有效的治疗策略可转化为临床环境。研究阐明了微量营养素（例如维生素、氨基酸）在缓解诱发的神经退行性变，导致宿主认知能力下降，从而阐明微量营养素- 依赖方法可能会减轻宿主记忆丧失，维生素 B12 (VB12) 是维持记忆的关键因素。肠上皮平衡和功能性微生物生理学对抗诱导的毒性炎症。相比之下，VB12 缺乏会使致病性炎症持续存在，最终导致肠道功能的破坏。此外，我们还发现 VB12 具有调节 Tregs、小胶质细胞和大脑的功能。脂质组，所有这些都可以控制诱导的神经炎症，以进一步深入研究 VB12 的功能能力。维持大脑 Tregs 潜在地控制 tau 病病理学，该管理的目标补充研究计划是进一步阐明 VB12 参与大脑功能的硬连线 Tregs 限制小胶质细胞不受控制的激活，可能与 tau 蛋白病依赖性记忆衰退有关。我们的假设是 VB12 紧密维持大脑 Treg 稳态，以限制 tau 蛋白病相关的神经炎症，导致宿主记忆丧失显着改善，具体目标是： 1. 研究 VB12 在维持功能性脑 Tregs 以限制 tau 病病理学方面的相关性，以及 2. 阐明 Tregs 对小胶质细胞的调节，可能有助于改善记忆本次行政补充研究提案的预计结果将是首次深入研究。关于 VB12 通过功能性 Tregs 调节大脑稳态以潜在减少宿主的报告记忆力下降。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Composition of the gut microbiota transcends genetic determinants of malaria infection severity and influences pregnancy outcome.

肠道微生物群的组成超越了疟疾感染严重程度的遗传决定因素并影响妊娠结局。

DOI：
发表时间：
2019-06
期刊：
影响因子：
11.1
作者：
Morffy Smith, Catherine D;Gong, Minghao;Andrew, Alicer K;Russ, Brittany N;Ge, Yong;Zadeh, Mojgan;Cooper, Caitlin A;Mohamadzadeh, Mansour;Moore, Julie M
通讯作者：
Moore, Julie M

Regulation of Th17 cells by P. UF1 against systemic Listeria monocytogenes infection.

P.UF1 对 Th17 细胞的调节，抵抗系统性单核细胞增生李斯特菌感染。

DOI：
发表时间：
2018
期刊：
影响因子：
12.2
作者：
Colliou, Natacha;Ge, Yong;Gong, Minghao;Zadeh, Mojgan;Li, Jing;Alonzo 3rd, Francis;Mohamadzadeh, Mansour
通讯作者：
Mohamadzadeh, Mansour

Neonatal intestinal immune regulation by the commensal bacterium, P. UF1.

共生细菌 P. UF1 的新生儿肠道免疫调节。

DOI：
发表时间：
2019-03
期刊：
影响因子：
8
作者：
Ge, Yong;Gong, Minghao;Colliou, Natacha;Zadeh, Mojgan;Li, Jing;Jones, Dean P;Li, Shuzhao;Mohamadzadeh, Mansour
通讯作者：
Mohamadzadeh, Mansour

Regulating colonic dendritic cells by commensal glycosylated large surface layer protein A to sustain gut homeostasis against pathogenic inflammation.

通过共生糖基化大表面层蛋白 A 调节结肠树突状细胞，维持肠道稳态，对抗致病性炎症。

DOI：
发表时间：
2020-01
期刊：
影响因子：
8
作者：
Ge, Yong;Gong, Minghao;Zadeh, Mojgan;Li, Jing;Abbott, Jeffrey R;Li, Wei;Morel, Laurence;Sonon, Roberto;Supekar, Nitin T;Azadi, Parastoo;Wang, Yating;Jones, Dean P;Li, Shuzhao;Mohamadzadeh, Mansour
通讯作者：
Mohamadzadeh, Mansour

Regulating vitamin B12 biosynthesis via the cbiMCbl riboswitch in Propionibacterium strain UF1.

通过丙酸杆菌菌株 UF1 中的 cbiMCbl 核糖开关调节维生素 B12 生物合成。