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

基本信息

批准号：
10284863
负责人：
Amin Arbabian
金额：
$ 23.63万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
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/10284863
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 Miniaturization 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 Ultrasonography Unhealthy Diet Wireless Technology 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 molecular marker monitoring device new technology novel oxidation prevent response sensor small molecule tool treatment strategy

项目摘要

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.

项目概要非传染性疾病 (NCD)，包括肥胖、2 型糖尿病、炎症性肠病（IBD），癌症给全球经济和生活质量带来了巨大的负担。许多非传染性疾病，特别是胃肠道疾病，都受到肠道菌群相互作用的影响将微生物、生活方式和非传染性疾病联系起来的一个主要假设是：不健康的饮食和抗生素的使用会选择促进肠道化学氧化的微生物。破坏宿主和微生物组的稳态，导致不适当的、自我强化的免疫和代谢然而，定量假设检验目前是不可能的，因为研究人员缺乏直接测试模型生物（大鼠和小鼠）肠道氧化的必要工具，现有数据是相关的或相关的。依赖不精确的措施（例如基因消融和竞争实验）阻碍实验研究微生物群的变化如何导致疾病。我们的提案概述了体内实时自动测量平台的开发该平台包括可植入/可摄入的氧化还原电位 (ORP)。传感器和可穿戴数据收集设备是化学环境的综合测量。失去或获得电子的倾向，或者换句话说，它被氧化或还原的倾向。将 ORP 传感应用于小鼠和人类的粪便样本，证明抗生素引起的 ORP 变化虽然这些结果强烈表明肠道氧化在其中起着致病作用。病理生理学方面，粪便 ORP 与肠道生理状况的相关性尚不清楚。我们为我们的工作提出了两个主要目标，以解决现有的离体技术局限性，并促进更好地了解肠道氧化还原病理生理学：1）开发技术以实现体内长期自动化清醒啮齿动物的 ORP 测量，2) 确定微生物组的变化如何影响体内 ORP，以及确定肠道氧化还原状态的特定化学相关性为了实现这些目标，我们将使用新型超声波。唤醒和电流耦合技术，克服设备小型化的根本挑战用于植入啮齿动物胃肠道，对动物运动和内部装置运动的鲁棒性，以及数据收集自动化，用于实用、可扩展的实验。这项工作意义重大，因为识别肠道氧化还原状态即将发生的变化的新工具已经出现可能通过测试该领域的一个重要的新兴假设来推进基础科学。这项研究所需的技术进步使得探索诊断的氧化还原模式成为可能，并且治疗与氧化还原失衡相关疾病的策略，为翻译工作。