Elucidating the Host Metabolic Response to Consumption of Kombucha-associated Microorganisms

阐明宿主对康普茶相关微生物消耗的代谢反应

基本信息

批准号：
10678132
负责人：
Rachel Nell Dumez
金额：
$ 3.88万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10678132
关键词：
16S ribosomal RNA sequencing Address Adenosine Monophosphate Aging Animal Model Animals Beverages Binding Sites Biochemical Biological Biological Assay Biological Models Biological Process Caenorhabditis elegans Carbon Cells Communities Complement Complementary Health Complex Consumption Data Diet Environmental Risk Factor Escherichia coli Etiology FRAP1 gene Fatty Acids Fatty acid glycerol esters Fermentation Food Gastrointestinal tract structure Gene Expression Genes Genetic Genetic Transcription Genomic approach HNF4A gene Health Health Benefit Health Promotion Homeostasis Human Immune response Individual Ingestion Insulin Integrative Medicine Investigation Laboratories Lipids Lipolysis Longevity Marketing Measures Metabolic Metabolic Pathway Metabolism Methods Microbe Modeling Molecular Mutation Nematoda Nuclear Ontology Oxidoreductase Pathway interactions Persons Phenotype Physiological Physiological Processes Physiology Play Population Preventive care Probiotics Process Protein Kinase Reporter Role Safety Shapes Signal Pathway Signal Transduction Source Stains Standardization System Tea Testing Thinness Transcriptional Regulation United States Volatile Fatty Acids commensal microbes detection of nutrient dietary control differential expression experimental study genetic approach genetic regulatory protein gut microbes gut microbiome host-microbe interactions human subject in vivo insight lipid metabolism longevity gene mRNA sequencing metabolic abnormality assessment microbial microbial community microbiome microorganism mutant oxidation promoter response transcription factor transcriptome transcriptomics

项目摘要

PROJECT SUMMARY Kombucha is a popular fermented tea that contains probiotics. This beverage has seen a surge in popularity in the United States since the turn of the century and is purported to have many health benefits. Some of these health claims have been cursorily examined, however, none have been rigorously tested and the mechanistic interactions between the microbial components of Kombucha and the host remains unexplored. I will elucidate the host metabolic response to consumption of Kombucha-associated microbes (K. microbes), thereby informing its use in complementary health approaches. The impact of individual probiotic microbes on human health is difficult to deconvolute as humans consume a complex diet, have trillions of gut microbes (including many unidentified species), and measuring host-microbe interactions is not feasible in human subjects. Therefore, animal model systems are essential to investigate the effects of consuming probiotics, including those in Kombucha, on host physiological processes. Caenorhabditis elegans is an excellent model system to explore how K. microbes modulate the host pathways that govern lipid homeostasis, because their microbiomes are easily manipulated through the food source provided and they are a well-established system to study metabolism and the aging process in vivo. I have established a standardized method to maintain C. elegans on a diet exclusively consisting of K. microbes that is consistent with the community found in the fermenting culture (confirmed through 16S rRNA sequencing). In preliminary investigations, I observed that populations of C. elegans exclusively consuming K. microbes, as compared to a control diet (E. coli, the standard laboratory food source), have altered expression of core lipid metabolism genes (e.g., beta-oxidation, fatty acid desaturation), decreased fat levels, and an increased median lifespan. Critically, the molecular mechanisms by which K. microbes alter host physiology is completely unknown. Therefore, I plan to use molecular and genetic approaches in C. elegans to systematically identify the molecular mechanisms that govern the host response to K. microbe consumption and elucidate the components of Kombucha that are necessary and sufficient to confer the observed metabolic and lifespan phenotypes. The proposed experiments will provide unprecedented insight into the mechanism by which K. microbe consumption reconfigures host metabolism.

项目摘要康普茶是一种受欢迎的发酵茶，含有益生菌。这种饮料在自本世纪初以来，美国被认为具有许多健康益处。其中一些但是，对健康声明进行了修复的检查，但是，没有进行严格测试和机械。康普茶的微生物成分与宿主之间的相互作用尚未探索。我会阐明宿主代谢对康普茶相关微生物（K. Microbes）的消费的反应，从而告知它用于互补的健康方法。个体益生菌微生物对人类健康的影响是当人类食用复杂的饮食时，很难被宣传，有数万亿个肠道微生物（包括许多身份不明的物种），在人类受试者中测量宿主 - 微生物相互作用是不可行的。所以，动物模型系统对于研究食用益生菌的影响至关重要，包括康普茶，在宿主生理过程中。秀丽隐杆线虫是探索的绝佳模型系统 K.微生物如何调节控制脂质稳态的宿主途径，因为它们的微生物组为通过提供的食物来源轻松操纵，它们是研究新陈代谢的完善系统和体内衰老过程。我已经建立了一种标准化的方法来维持秀丽隐杆线虫的饮食由K.微生物组成，与发酵文化中的社区一致（通过16S rRNA测序确认）。在初步研究中，我观察到C. 与对照饮食相比，秀丽隐杆线虫专门消费K. Microbes（大肠杆菌，标准实验室食品来源），核心脂质代谢基因的表达改变了（例如β-氧化，脂肪酸去饱和），脂肪水平降低，中位寿命增加。至关重要的是，k的分子机制。微生物改变宿主生理是完全未知的。因此，我计划使用分子和遗传秀丽隐杆线虫中的方法有系统地确定控制宿主对宿主反应的分子机制 K.微生物的消耗和阐明康普茶的组成部分，足以授予观察到的代谢和寿命表型。拟议的实验将提供前所未有的见解 K. Microbe消耗重新配置宿主代谢的机制。