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

• 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
• 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

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.

项目概要 康普茶是一种流行的发酵茶，含有益生菌。这种饮料在 自世纪之交以来的美国，据称具有许多健康益处。其中一些 健康声明已被粗略审查，但没有经过严格测试，其机制 康普茶的微生物成分与宿主之间的相互作用仍有待探索。我会解释一下 宿主对康普茶相关微生物（K. microbes）消耗的代谢反应，从而告知 它在补充健康方法中的应用。个别益生菌对人类健康的影响是 由于人类饮食复杂，肠道微生物有数万亿个（包括许多 不明物种），并且测量宿主与微生物的相互作用在人类受试者中是不可行的。所以， 动物模型系统对于研究食用益生菌的影响至关重要，包括那些 康普茶，对宿主生理过程的影响。秀丽隐杆线虫是一个极好的探索模型系统 K. 微生物如何调节控制脂质稳态的宿主途径，因为它们的微生物群是 通过提供的食物来源很容易操纵，它们是研究新陈代谢的完善系统 以及体内的衰老过程。我已经建立了一种维持秀丽隐杆线虫饮食的标准化方法 完全由 K. 微生物组成，与发酵培养物中发现的群落一致 （通过16S rRNA测序证实）。在初步调查中，我观察到 C. 与对照饮食（大肠杆菌，标准实验室食品）相比，线虫只消耗 K. 微生物 来源），改变了核心脂质代谢基因的表达（例如，β-氧化、脂肪酸去饱和）， 降低脂肪水平，延长中位寿命。至关重要的是，K. 微生物改变宿主生理机能的情况完全未知。因此，我打算利用分子和遗传学的方法 在线虫中系统地识别控制宿主反应的分子机制 K.微生物消耗并阐明康普茶的必要且充分的成分 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 研究K.微生物消耗重新配置宿主代谢的机制。