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Vitamin A metabolizing activity of the gut microbiome.

肠道微生物组的维生素 A 代谢活性。

基本信息

批准号：
10628029
负责人：
Shipra Vaishnava
金额：
$ 23.96万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-25 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10628029
关键词：
Bacteria Body Patterning Cell Cycle Cell Death Cell Differentiation process Cell Maturation Cells Cessation of life Communication Complement Complex Diet Disease Embryo Enterocytes Enzymes Epithelial Cell Proliferation Epithelial Cells Equilibrium Generations Genes Genetic Transcription Germ-Free Gut Mucosa Homeostasis Homing Human Human Genome Immunity Infection Inflammation Intestinal Mucosa Intestines Lactobacillus Length Liver Lymphocyte Malignant Neoplasms Mediating Metabolic Metabolism Microbe Micronutrients Modeling Mucous Membrane Mus Natural regeneration Nutrient Organoids Physiology Play Predisposition Proliferating Receptor Signaling Regenerative capacity Retinoic Acid Receptor Retinoids Role Signal Transduction Source Symbiosis Transcription Initiation Tretinoin Villus Vitamin A Vitamin B Complex Work aldehyde dehydrogenases bacterial community base colon microbiota commensal bacteria crypt cell dietary gut bacteria gut microbiome gut microbiota host microbiome immune function intestinal crypt intestinal epithelium microbial microbial community microbiota novel programs regenerative stem cell niche stem cell proliferation

项目摘要

Project Summary: The human and mouse colonic microbiota is a large and complex microbial community. The gene set of the gut microbiota (the gut microbiome) is estimated to be about 3 million genes ~150 times larger than that of the human genome. This large and diverse microbial community has an equally extensive metabolic repertoire that complements the activity of mammalian enzymes in the liver and gut mucosa however its role in metabolizing intestinal vitamin A has not been explored. Vitamin A, a diet derived nutrient, is key for regulating multiple aspects of immunity and susceptibility to infections. Effect of vitamin A are coordinated via its metabolite retinoic acid (RA), a potent regulator of cellular transcriptional program. RA signaling in the lymphocytes is required for initiating transcriptional programs that guide their homing to the mucosal tissue as well their cell-fate transitions in the intestinal mucosa. Additionally, RA signaling is critical for maintaining plasticity of intestinal epithelium, allowing them to dedifferentiate and replenish the pool of cycling cells that are lost upon damage. We find that gut lumen of conventional mice has much higher RA levels while in germ-free state RA levels are undetectable in the lumen. Moreover, we find that gut bacteria show strong activity for aldehyde dehydrogenase, a key rate limiting enzyme that is responsible for conversion of vitamin A to RA. Finally, we identify Lactobacillus spp in the mouse gut microbiome as bacterial taxa possessing vitamin A metabolic activity. We hypothesize that gut microbiome is a novel and potent source of vitamin A metabolic activity that plays a crucial role in regulating levels of metabolically active retinoids in the gut and regulates vitamin A dependent host physiology in the intestine and beyond. In this proposal we will explore the potential of gut microbiome to metabolize dietary vitamin A into RA and its effect on the mammalian host.

项目总结: