Oxidative status as a predictor of disease activity and response to therapy in pediatric patients with inflammatory bowel disease
Mazra, Armaan F.
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INTRODUCTION: Inflammatory Bowel Disease (IBD) is a multifactorial chronic relapsing condition thought to be caused by an interplay between a patient’s genetics, immune system, and susceptibility to environmental factors. Oxidative Stress (OS) is one pathogenic mechanism driving the inflammation and tissue damage observed in patients with IBD. OS in IBD is mediated by an overwhelming abundance of reactive oxygen and nitrogen species (RONS) generated by activated immune cells, including neutrophils and macrophages, that have been recruited to the intestinal mucosa. The relative abundance of RONS is assessed using technology capable of directly measuring the ambient oxidative-reductive potential (ORP) in tissue or a fluid sample. ORP values can provide new approaches that link disease pathogenesis with treatment. ORP assessment may prove to be a sensitive, inexpensive, and non-invasive biological marker in the diagnosis and interval assessment of patients with IBD. OBJECTIVES: The goal of this study was to assess the relationship between disease activity and oxidative-reductive potential (ORP) in the stool and urine of patients with and without IBD. METHODS: Patients admitted to Boston Children’s Hospital (Boston, MA) were recruited and consented to participate in this study. Stool and urine samples were collected, and the ORP (mV) was measured using the Arrowdox, PCE, and Redoxsys devices. Samples were collected between the period of November 2018 and March 2021. RESULTS: The data demonstrate that measuring the ORP of stool supernatants may be a useful biomarker for assessing disease activity in patients with IBD. The several phases of this study include addressing (1) the accuracy, reliability, and validity of ORP measurements in stool and urine (2) establishing methods that provide consistent intra- and inter-device readings. These findings ultimately led to the measurement of stool supernatant & pellet using the Arrowdox and Redoxsys platforms. Data collected demonstrate a relationship between ORP (mV) measurements of stool supernatants and increased disease activity in patients with IBD. CONCLUSION: The measurement of ORP in the stool of patients with and without IBD may be a reliable tool for indicating clinical disease status. Stool supernatant ORP readings appear to provide the most consistent intra- and inter-device readings. The future of developing this technology study will focus on amplifying patient recruitment to more definitively assess the relationship between stool ORP measurement and disease activity in patients with and without IBD. Urine ORP values may not reflect disease activity in patients with IBD. However, further studies that focus on how urine ORP changes over time and under certain conditions (2°C, 20°C, and -80°C) are necessary. A more thorough understanding of the impact of diet, gut aerobic and anaerobic bacterial makeup, and hematochezia prevalence on redox status is also needed to control for potentially confounding variables. The ability to reliably measure redox measurements will support clinical trials assessing candidate antioxidant therapies.