A Pilot Study on the Effect of Colesevelam on the Microbiome in Primary Terminal Ileal Resected Crohn's Disease

Abstract

Background: Surgery plays a pivotal role in ileal Crohn's disease despite the risk of endoscopic recurrence following an ileocaecal resection greater than 65% within 12 months of surgery. More than 90% of Crohn's patients have a concomitant diagnosis of bile acid diarrhoea following an ileal resection. This pilot study aimed to assess whether the use of bile acid sequestrants in post-operative Crohn's patients with bile acid diarrhoea can alter the microbiome and prevent disease recurrence. Method(s): Post-operative Crohn's patients with symptoms of diarrhoea underwent 75SeHCAT testing for bile acid diarrhoea. If positive (75SeHCAT < 15%), patients were treated with colesevelam and stool samples were collected at 4-weeks, 8-weeks and 6-12 months posttreatment. If negative (75SeHCAT > 15%), treatment was not given and were reviewed in clinic as per local guidelines. Patients underwent a 6-12 months post-operative colonoscopy where mucosal biopsies were taken. Disease activity was established using the endoscopic Rutgeert's score, with disease remission defined as Rutgeerts score < i2 and disease recurrence 3 i2. Faecal and mucosal 16S ribosomal RNA gene analysis was undertaken to assess a/b-diversity and microbial composition. Result(s): A total of 44 faecal samples and 44 mucosal biopsies were sequenced from 14 patients. 1/10 patients on colesevelam and 2/4 patients not on colesevelam demonstrated disease recurrence. There was no significant difference in a/b-diversity pre- and post-treatment. Pre-treatment, the three most abundant bacterial classes in all patients were Bacteroidia, Clostridia and Gammaproteobacteria (Figure 1). Following 6-12 months of treatment, out of the 9 patients on colesevelam, 5/9 (55.6%) had a reduction in Bacteroidia, 9/9 (100%) had an increase in Clostridia, and 7/9 (77.8%) had a reduction in Gammaproteobacteria. Of the two patients not given colesevelam, 1/2 (50%) showed a reduction in Bacteroidia, increase in Clostridia and a reduction in Gammaproteobacteria. Conclusion(s): This small pilot study demonstrated that patients who were given colesevelam, a bile acid sequestrant, were more likely to be in disease remission at their 6-12 months colonoscopy review. Furthermore, treatment with colesevelam may have a role in altering the microbiome to help maintain remission states in post-operative Crohn's disease. Larger mechanistic studies are now needed to confirm these findings and demonstrate statistical significance.