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.

项目总结 康普茶是一种受欢迎的含有益生菌的发酵茶。这种饮料在中国大受欢迎。 自世纪之交以来一直是美国人的食物，据称对健康有许多好处。其中一些 健康声明已经被粗略地检查过了，然而，没有一个经过严格的测试和机械的 康普茶的微生物成分与寄主之间的相互作用尚不清楚。我会澄清的 宿主对消耗与康普茶相关的微生物(K.微生物)的代谢反应，从而告知 它在补充性保健方法中的使用。个别益生菌对人类健康的影响是 很难解体，因为人类饮食复杂，有数万亿的肠道微生物(包括许多 未知物种)，而且在人类受试者中测量宿主-微生物相互作用是不可行的。因此， 动物模型系统对于研究食用益生菌的影响是必不可少的，包括 康普茶对寄主生理过程的影响。秀丽隐杆线虫是一个值得探索的优秀模式系统 克雷伯氏菌如何调节控制脂质稳态的宿主途径，因为它们的微生物群 很容易通过提供的食物来源进行操作，它们是研究新陈代谢的良好系统 以及体内的衰老过程。我已经建立了一种标准化的方法来维持线虫的节食 完全由K-微生物组成的，与在发酵培养中发现的群落一致 (经16S rRNA测序证实)。在初步调查中，我观察到C. 与对照饮食(标准实验室食物--大肠杆菌)相比，仅摄取克雷伯氏菌的秀丽动物 来源)，改变了核心脂肪代谢基因的表达(例如，β-氧化、脂肪酸减饱和)， 降低脂肪水平，延长中位寿命。重要的是，K。 微生物对宿主生理的改变是完全未知的。因此，我计划使用分子和基因 线虫系统识别控制寄主反应的分子机制的方法 K.微生物消耗，并阐明康普茶的必要和足够的成分，以授予 观察到的代谢和寿命表型。拟议中的实验将提供前所未有的洞察力 K微生物消耗重新调整宿主新陈代谢的机制。