Assessment of LGR5 Expression in Colonic Biopsies of Patients with Chronic Diarrhea of Unknown Origin

Background: Chronic diarrhea of unknown origin (CDUO) presents a diagnostic challenge due to the absence of clear histological or inflammatory findings. Emerging evidence suggests that intestinal stem cell dysfunction may contribute to mucosal abnormalities. This study aimed to assess the expression of LGR5 in colonic biopsies of patients with CDUO compared to healthy controls. Methods: A comparative cross-sectional study was conducted at Khalifah Gul Nawaz Teaching Hospital, Bannu, from January to June 2025. A total of 120 participants were enrolled, including 60 cases of CDUO and 60 age-matched controls. Colonic biopsies were obtained during colonoscopy, and LGR5 expression was evaluated using immunohistochemistry and scored semi-quantitatively (0 to 3+). Data were analyzed using SPSS version 26, with a significance level of p ≤ 0.05. Results: Among cases, 66.7% had low LGR5 expression (score 0–1+), compared to only 16.7% in controls. High LGR5 expression (score 2+–3+) was observed in 33.3% of cases versus 83.3% of controls. Strong staining (>50% cells) was seen in only 10% of cases compared to 50% of controls. The difference in LGR5 expression between groups was statistically significant (p < 0.0001). Conclusion: LGR5 expression was significantly reduced in patients with CDUO, suggesting potential intestinal stem cell dysfunction. LGR5 may serve as a useful biomarker for identifying subclinical mucosal defects in unexplained chronic diarrhea.