Elevated serum glutathione reflects endoscopic disease activity in inflammatory bowel disease

Redox imbalance and systemic oxidative stress are implicated in the pathophysiology of inflammatory bowel disease (IBD). Oxidative stress previously demonstrated strong associations with endoscopic disease activity in IBD. In this study, we aimed to prospectively evaluate a panel of redox proteins, including circulating total free thiols (FTs), low-molecular-weight thiols, and thioredoxin-1, as biomarkers for endoscopic disease activity in IBD.

Patients with IBD (n = 111) undergoing surveillance endoscopy were enrolled. Blood was collected at endoscopy along with clinical and biochemical assessments. Endoscopic activity was graded using the Mayo endoscopic score for ulcerative colitis (UC) or the Simple Endoscopic Score for Crohn's disease (SES-CD) (CD). Serum and plasma biomarkers (FTs, glutathione (GSH), ischemia-modified albumin (IMA), homocysteine, cysteine, thioredoxin-1) were analyzed. Logistic regression was used to test associations with disease activity, adjusting for relevant confounders.

Among all biomarkers, only serum GSH significantly associated with active endoscopic disease (adjusted odds ratio (OR) per doubling: 4.19, p = 0.04). This was most evident in CD, but not significant in UC. IMA only showed a univariable association (p < 0.05). ROC analysis identified GSH as the most accurate oxidative stress marker (AUC = 0.71 in CD; 0.65 in UC). All were outperformed by fecal calprotectin (AUC = 0.77). However, combining calprotectin with oxidative stress markers substantially improved discrimination (AUC = 0.95). Finally, Trx1 and FTs were significantly increased in patients with colonic disease activity (p < 0.05).

Serum GSH may serve as a systemic biomarker of endoscopic disease activity in IBD, particularly CD. While less accurate than fecal calprotectin alone, systemic oxidative stress markers strongly enhance its diagnostic performance, suggesting complementary value for disease monitoring.