Altered Levels of Enteric Glial Cells and Their Associated Pro‐Inflammatory Proteins in Patients With Ulcerative Colitis During Active Disease Compared to Remission and Healthy Controls

ABSTRACT Background Enteric glial cells (EGC) play a crucial role in gut barrier maintenance but their role in ulcerative colitis (UC)‐related inflammation is largely unknown. This study investigated EGC and related proteins in patients with UC in inflamed and non‐inflamed segments during clinically active disease and remission following anti‐inflammatory treatment. Methods Colorectal biopsies were obtained from inflamed and non‐inflamed segments of 14 patients with UC before and after initiating anti‐inflammatory therapy and achieving clinical and endoscopic remission. Control biopsies were collected from 16 healthy controls (HC). EGC markers: glial fibrillary acidic protein (GFAP + ) and S100 calcium‐binding protein β (S100β + ) were assessed by immunofluorescence. Relative estimates of inflammatory proteins in biopsies were analyzed using Olink technology. The EGC cell line CRL‐2690 was exposed to interleukins (IL)‐4 and IL‐6 at varying concentrations and durations, and analyzed by western blotting. Results EGC GFAP+ and EGC S100β+ were more abundant in inflamed colonic segments during active UC compared to remission ( p < 0.001) and HC ( p < 0.0001). In non‐inflamed segments, EGC GFAP+ decreased significantly with remission ( p < 0.001), whereas EGC S100β+ remained stable. Interleukin stimulation modulated GFAP expression in vitro, with IL‐6 increasing and IL‐4 decreasing in a dose and time‐dependent manner. EGC‐associated proteins, including cytokines, neurotrophic factors and chemokines were elevated in inflamed segments during active UC, normalizing towards HC levels upon remission. Conclusion Elevated EGC counts, and associated pro‐inflammatory proteins characterize inflamed mucosa during clinical active UC. These novel findings suggest that EGC may be clinically relevant for identifying novel biomarkers for disease monitoring.