Gut Flora Predicts Postoperative Crohn’s Disease Recurrence

TOPLINE:

Distinctly different microbial signatures across ileal and colonic mucosa both precede and predict Crohn’s disease recurrence in patients who achieve surgical remission.

METHODOLOGY:

• Some microbial features of mucosa-associated microbiota obtained from resected ileal specimens have been associated with recurrence in patients with Crohn’s disease. However, no studies had analyzed microbial profiles in patients while they were in surgically induced remission to identify signatures that could predict recurrence.
• Researchers prospectively recruited a multicenter cohort of 262 patients with Crohn’s disease undergoing ileocolonic resection (median age at surgery, 32 years; 46.6% women).
• Overall, 944 biopsy samples from the neoterminal ileum, colon, and rectosigmoid were obtained from 349 postoperative colonoscopies.
• Microbial DNA was extracted from the biopsy samples for 16S rRNA gene sequencing, and 15,345,941 high-quality 16S rRNA sequences were generated. Microbial diversity and taxonomic differential relative abundance were analyzed.
• The Rutgeerts score was evaluated during each postoperative colonoscopy, with a score of ≥ i2 indicating endoscopic recurrence.

TAKEAWAY:

• Ninety-seven patients showed endoscopic remission at the first postoperative colonoscopy. Of those patients, 25 (25.8%) developed endoscopic recurrence and 72 (74.2%) remained in remission at the second colonoscopy.
• The ileal microbiota obtained at the first colonoscopy showed lower alpha diversity, assessed using the Chao1 index, in patients who developed recurrence at the second colonoscopy than in those who remained in remission (P < .05).
• Patients who developed recurrence showed a reduction in the genus Anaerostipes, whose species can produce short-chain fatty acids that play a crucial role in gut homeostasis, at the three biopsy sites. In contrast, several genera from the class Gammaproteobacteria (Klebsiella and Escherichia-Shigella), which could induce intestinal inflammation, were enriched.
• Inclusion of the result from the ileal and colonic mucosa–associated microbiota analysis improved the prediction of recurrence risk compared with the use of clinical data alone, especially for rectosigmoid samples, with an area under the curve (AUC) of 83.1% for microbiome plus clinical data vs 68% for clinical data only, and for neoterminal ileum samples, with respective AUCs of 79.5% vs 56.4%.

IN PRACTICE:

“Using several of the taxa positively and negatively associated with recurrence, we were able to improve the prediction of future endoscopic recurrence compared to known clinical risk factors of postoperative CD [Crohn’s disease] recurrence, such as smoking and anti-TNF prophylaxis. A minimally invasive flexible sigmoidoscopy could be used to assess the microbial biomarkers described in rectosigmoid mucosa in our study to predict recurrence,” the authors wrote.

SOURCE:

This study, led by Cristian-Hernandez Rocha, MD, from the Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile in Santiago, Chile, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

The sample size of the study, especially for patients with postoperative endoscopic remission, was relatively small. Although expert endoscopists assigned each score, the lack of endoscopy central reading in the study could introduce bias. Researchers only performed an internal validation of the random forest model, which limited the generalizability of the study findings.

DISCLOSURES:

The National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health supported this study. The authors declared no conflicts of interest.