Influence of proton pump inhibitor intake on the course of ulcerative colitis in patients with concomitant GERD

Abstract

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease of the large intestine. Among the potential factors that may lead to remission breakdown and UC exacerbation is the intake of medications by patients for comorbid conditions. One such condition for which patients with UC may be prescribed proton pump inhibitors (PPIs) is gastroesophageal reflux disease (GERD). PPI intake in patients with UC may be associated with worsening clinical symptoms, as well as laboratory and endoscopic changes. Although the exact mechanisms remain unclear, multiple studies suggest that PPIs can negatively influence the gut microbiota, reduce beneficial bacteria such as Bifidobacterium, and promote the overgrowth of opportunistic organisms including Enterobacteriaceae, Clostridioides difficile, Salmonella, and Escherichia-Shigella. Moreover, PPIs may alter bile acid metabolism and reduce short-chain fatty acids while increasing the level of toxic compounds such as hydrogen sulfide, thus contributing to mucosal inflammation. Structural changes in epithelial cells, including cytoskeletal alterations and weakened barrier function, have also been reported, facilitating microbial translocation and triggering colonic inflammation. Purpose. To retrospectively analyze the effect of PPI intake on the course of UC in patients with comorbid GERD. Materials and methods. We conducted a retrospective comparative study at the Department of Internal Medicine №1 of Bogomolets National Medical University from September 2024 to December 2025. The study involved 40 patients (30 men/10 women) with histologically confirmed UC and comorbid GERD. Patients were divided into two groups based on PPI intake. The first group (n=20) received PPIs once daily for 12 weeks in addition to standard UC therapy. The second group (n=20) underwent lifestyle modification without PPI use. GERD was diagnosed based on clinical symptoms (heartburn ≥2 times per week), endoscopic findings per the Los Angeles classification (grades B–D), and 24-hour pH impedance monitoring (DeMeester score >14.7 or acid exposure time >6%). The UC course was evaluated using the PRO2 scale, fecal calprotectin levels, and colonoscopy findings with the Mayo Endoscopic Score (MES) at baseline and after 4, 8, and 12 weeks. Results. At baseline, both groups were comparable in terms of age, sex distribution, and initial clinical/laboratory parameters, including fecal calprotectin levels and PRO2 scores. After 4, 8, and 12 weeks, patients receiving PPIs demonstrated a consistent increase in fecal calprotectin: 65, 120, and 180 μg/g respectively, compared to stable normal levels in the non-PPI group (p<0.05). According to the PRO2 scale, patients in the PPI group showed clinical deterioration, with increased daily stool frequency and the presence of blood in stool (scores of 2+2) by week 12, while the control group maintained stable scores (0–1). Endoscopic assessment revealed worsening mucosal inflammation in the PPI group: by week 12, MES scores of 1–2 were recorded, indicating mild to moderate inflammation, compared to MES 0 (remission) in the non-PPI group. Conclusions. PPI use in UC patients with comorbid GERD adversely affects clinical outcomes, as well as laboratory and endoscopic indicators of disease activity. The findings suggest that PPI therapy may contribute to relapse or flare-ups in UC, possibly due to alterations in gut microbiota and mucosal immune response. Further prospective studies with microbiota profiling and larger cohorts are needed to elucidate the mechanisms and determine optimal management strategies for GERD in patients with inflammatory bowel diseases.