In vivo Wireless Sensors for Gut Redox Monitoring to Understand Host and Microbe Physiology

用于肠道氧化还原监测的体内无线传感器，以了解宿主和微生物的生理学

• 批准号: 10427439
• 负责人: Amin Arbabian
• 金额: $ 19.75万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10427439
• 关键词: Ablation; Acute; Address; Affect; Agreement; Air; Animal Model; Animals; Antibiotic Therapy; Antibiotics; Automation; Bacteria; Basic Science; Chemicals; Child; Coupling; Data; Data Collection; Development; Devices; Diagnosis; Diet; Discipline; Disease; Electrons; Environment; Equilibrium; Functional disorder; Future; Gases; Gastrointestinal tract structure; Genetic; Goals; Health; Health Promotion; Homeostasis; Human; Hydrogen Peroxide; Immune; Immune system; Impairment; In Situ; Inflammatory Bowel Diseases; Intervention; Investigation; Large Intestine; Lead; Life Style; Link; Location; Malignant Neoplasms; Malnutrition; Marasmus; Measurement; Measures; Metabolic; Microbe; Monitor; Movement; Mus; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oxidants; Oxidation-Reduction; Oxides; Oxygen; Pathogenicity; Pattern; Physiological; Physiology; Play; Quality of life; Rattus; Research; Research Personnel; Rodent; Role; Sampling; Signal Transduction; Small Intestines; Sum; System; Techniques; Technology; Testing; Time; Translations; Ultrasonic wave; Unhealthy Diet; Work; awake; base; design; dysbiosis; experimental study; host microbiome; host-microbe interactions; immunoregulation; implantation; in vivo; in vivo monitoring; microbiome; microbiome alteration; microbiome composition; microbiota; miniaturized device; molecular marker; new technology; novel; oxidation; prevent; response; sensor; small molecule; tool; treatment strategy; ultrasound; wireless; wireless electronic; wireless sensor

PROJECT SUMMARY Non-communicable diseases (NCDs) including obesity, type 2 diabetes, inflammatory bowel diseases (IBDs), and cancer impose a staggering burden on global economies and quality of life. Evidence is mounting that many NCDs – particularly those of the gastrointestinal tract – are influenced by the interplay of the microbiome and the host immune system. A leading hypothesis connecting microbes, lifestyle, and NCDs is that an unhealthy diet and antibiotic use select for microbes that promote chemical oxidation in the gut. This oxidation disrupts host and microbiome homeostasis leading to inappropriate, and self-reinforcing, immune and metabolic dysregulation. However, quantitative hypothesis testing is currently impossible because researchers lack the necessary tools to directly test gut oxidation in model organisms (rats and mice). Existing data is correlative or relies on imprecise measures (e.g. genetic ablation and competition experiments) preventing experimental study of how changes in the microbiota lead to disease. Our proposal outlines the development of a platform for real-time automated measurement of in vivo gut oxidation in rodents. The platform comprises implantable / ingestible Oxidation Reduction Potential (ORP) sensors and a wearable data collection device. ORP is an integrated measure of a chemical environment’s propensity to lose or gain electrons, or in other words its tendency to get oxidized or reduced. Recent work has applied ORP sensing to fecal samples from mice and humans, demonstrating ORP changes due to antibiotics and acute malnutrition. While these results are strongly suggesting of a causative role for gut oxidation in pathophysiology, the relevance of fecal ORP to gut physiological conditions is unclear. We propose two major aims for our work to address existing ex vivo technique limitations, and promote better understanding of gut redox pathophysiology: 1) Develop technology to enable long-term automated in vivo ORP measurements in awake rodents, 2) determine how changes to the microbiome affect in vivo ORP, and identify specific chemical correlates of the gut redox state. In achieving these goals, we will use novel ultrasound wake-up and galvanic coupling technologies to overcome the fundamental challenges of device miniaturization for implantation in the rodent GI-tract, robustness against animal movement and internal device movement, and data collection automation for practical, scalable experiments. This work is significant because new tools to identify impending changes in redox status in the gut are likely to advance basic science by testing a critical emerging hypothesis in the field. Simultaneously, the technological advances required for this study make it possible to explore redox patterns for diagnosis, and strategies for treatment, of diseases associated with redox imbalance, providing significant opportunities for translational work.

项目摘要 非传染性疾病（NCD），包括肥胖症，2型糖尿病，炎症性肠病 （IBD），癌症对全球经济和生活质量施加了惊人的燃烧。证据正在持续 许多NCD（尤其是胃肠道的NCD）都受到了相互作用的影响 微生物组和宿主免疫系统。连接微生物，生活方式和NCD的主要假设是 不健康的饮食和抗生素使用，用于促进肠道化学氧化的微生物。这种氧化 破坏宿主和微生物组稳态，导致不适当，自我增强，免疫和代谢 失调。但是，目前无法进行定量假设检验，因为研究人员缺乏 在模型生物（大鼠和小鼠）中直接测试肠道氧化的必要工具。现有数据是相关的或 依靠隐式测量（例如遗传消融和竞争实验）阻止了实验研究 微生物群的变化如何导致疾病。 我们的提案概述了一个实时自动化测量平台的开发 啮齿动物中的肠道氧化。该平台包括可植入 /可耐氧化降低电位（ORP） 传感器和可穿戴数据收集设备。 ORP是化学环境的综合度量 损失或获取电子设备的倾向，或者换句话说，它被氧化或减少的趋势。最近的工作有 将ORP传感应用于小鼠和人类的粪便样品，证明了由于抗生素而导致的ORP变化 和急性营养不良。尽管这些结果强烈暗示了肠道氧化的病因作用 病理生理学，粪便ORP与肠道生理状况的相关性尚不清楚。 我们提出了两个主要目标，以解决现有的离体技术限制，并促进 更好地了解肠道氧化还原病理生理学：1）开发技术以实现长期自动化体内 在清醒啮齿动物中的ORP测量值，2）确定微生物组的变化如何影响体内ORP，以及 确定肠氧化还原状态的特定化学相关性。在实现这些目标时，我们将使用新颖的超声波 唤醒和电耦合技术克服设备小型化的基本挑战 为了植入啮齿动物的啮齿动物诱饵，对动物运动和内部装置运动的鲁棒性，以及 用于实用，可扩展实验的数据收集自动化。 这项工作很重要，因为识别肠道氧化还原状态的新工具是 可能通过检验该领域的关键新兴假说来推进基础科学。同时， 这项研究所需的技术进步使得可以探索诊断的氧化还原模式，并 治疗策略，与氧化还原不平衡相关的疾病，为 翻译工作。