Investigation of oxidative status as a predictor of inflammatory bowel disease activity
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Abstract
INTRODUCTION: Inflammatory bowel disease (IBD) is a chronic condition affecting the gastrointestinal (GI) tract. A dysregulated release of reactive species by activated inflammatory cells recruited to the intestinal mucosa results in an ambient state of oxidative stress, which drives and sustains the mucosal inflammation and tissue damage observed in patients with active IBD. Direct measurement of the net redox status of body fluids may represent a novel biomarker to assist in the diagnosis and interval assessment of children and adults with IBD.
OBJECTIVES: This study explores the relationship between disease activity and oxidative status in patients with and without IBD.
METHODS: Patients treated in the ambulatory and inpatient setting at Boston Children's Hospital provided written informed consent and were enrolled in the study from July 2021 to February 2022. Stool, urine, blood, and ileal or cecal intestinal aspirates were collected. The redox potential was measured using three commercially available oxidation-reduction potential (ORP) measuring devices: RedoxSYS system, ArrowDOX, and Mettler Toledo probes.
RESULTS: The data suggest that the RedoxSYS system, ArrowDOX, and Mettler Toledo probes can reliably measure the redox status in the stool supernatant, urine, blood plasma, and intestinal aspirates collected from patients with and without IBD. The ArrowDOX probe had the smallest variability in the redox measurements of urine, whole blood, plasma, and intestinal aspirates compared to the RedoxSYS and Mettler Toledo probe. There is no significant difference in the redox status of samples from patients with Crohn’s disease stratified by the level of disease activity. There is a significant difference in the ArrowDOX redox measurements in stool supernatant from patients with mild as compared to severe ulcerative colitis. Further analysis of samples from patients with active ulcerative colitis shows that the ArrowDOX urinary redox values positively correlate with fecal calprotectin and lactoferrin. In contrast, the ArrowDOX stool supernatant redox measurements correlate with serum CRP and ESR. Mettler Toledo urinary redox values negatively correlate with serum CRP and ESR. There were no significant correlations between Mettler Toledo stool supernatant redox measurements with serum CRP, serum ESR, fecal calprotectin, and fecal lactoferrin. The urine and stool supernatant redox measurements with the ArrowDOX positively correlate with one another. In contrast, urine and stool redox measurements with Mettler Toledo poorly correlate. The PUCAI score positively correlates with the stool supernatant redox status obtained using the ArrowDOX and Mettler Toledo probes.
CONCLUSION: The increase in the number of study participants and sample types has allowed us to expand our evaluation of redox status in biosamples collected from patients with and without IBD. We have also gained valuable insights into the redox measurements across the biochemical samples and ORP-measuring devices. The data suggest that redox status measured in stool supernatant is more useful in assessing disease activity in patients with ulcerative colitis than in patients with Crohn’s disease. Increasing the sample size of patients with different levels of IBD activity, better understanding the impact of other factors on patient sample variability, and measuring the redox status of the same patients over time may show the potential of oxidative status as a novel biomarker of disease activity in IBD.
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Attribution-NonCommercial-NoDerivatives 4.0 International