Enteric glial cell remodeling at diagnosis is associated with reduced mucosal inflammation at follow-up in pediatric ulcerative colitis.

Enteric glial cells (EGCs) comprise a key component of the enteric nervous system (ENS), and there is currently no standardized approach to characterizing EGCs in human gastrointestinal (GI) disease. Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a group of chronic GI disorders in which predicting responsiveness to treatment is an ongoing challenge. We use glial-specific immunohistochemistry (IHC) for SOX10 to assess EGC patterns in IBD colon and whether these patterns correspond to early histologic outcomes in pediatric patients. Approximately half (22 of 47) of pediatric UC patients in our cohort demonstrate ectopically located non-basal glial aggregates (NBGAs) in colonic mucosa. Pediatric UC patients with NBGAs are more likely to exhibit improved mucosal pathology (OR 8.00, p = 0.0048) at approximately 1-year follow-up compared to UC patients without NBGAs. Patients with NBGAs show reduced Geboes Score and Nancy Histological Index values at follow-up compared to diagnosis (p = 0.011, p = 0.0071, respectively), while patients without NBGAs do not show reduced scores. UC patients with NBGAs are more likely to demonstrate reduced fecal calprotectin at follow-up compared to patients without NBGAs (OR 12.2, p = 0.01). These findings stratify pediatric UC patients based on EGC profiles and initial clinical course, and they may help guide therapeutic decisions early in disease. The study is the first to implement a routine approach to documenting EGCs in GI mucosal pathology.