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

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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.