Diarrhea in Crohn’s Disease: Investigating the Role of the Ileal Hormone Fibroblast Growth Factor 19

Background: Bile acids [BA] are usually reabsorbed by the terminal ileum, but this process is frequently abnormal in Crohn’s disease [CD]. BA malabsorption occurs, and excess colonic BA cause secretory diarrhea. Furthermore, the hormone fibroblast growth factor 19 [FGF19] is synthesized in the ileum in response to BA absorption and regulates BA synthesis. We hypothesized that reduced serum FGF19 levels will be associated with diarrheal symptoms and disease activity in both ileal-resected [IR-CD] and non-resected CD [NR-CD] patients. Methods: Fasting serum FGF19 levels were measured in 58 patients [23 IR-CD patients and 35 NR-CD patients]. Disease activity was assessed using the Harvey Bradshaw Index and C-reactive protein [CRP]. Stool frequency, Bristol Stool Form Scale and length of previous ileal resection were recorded. FGF19 levels were also compared with healthy and diarrhea control patients. Results: FGF19 levels were inversely correlated with ileal resection length in IR-CD patients [r = -0.54, p = 0.02]. In NR-CD patients, median FGF19 levels were significantly lower in patients with active disease compared with inactive disease [103 vs 158 pg/ml, p = 0.04] and in those with symptoms of diarrhea compared with those without [86 vs 145 pg/ml, p = 0.035]. FGF19 levels were inversely correlated with stool frequency, Bristol stool form and CRP in NR-CD patients with ileal disease. Conclusions: Reduced FGF19 levels are associated with ileal resection, diarrhea and disease activity. FGF19 may have utility as a biomarker for functioning ileum in CD. This study supports a potential role of FGF19 in guiding treatments for diarrhea in Crohn’s disease.