FECAL MICROBIOTA OF PEOPLE WITH CROHN’S DISEASE DOES NOT CHANGE WITH ILEOCECAL RESECTION

Abstract

Abstract INTRODUCTION Up to 80% of people with ileal Crohn’s disease (CD) will require an ileocecal resection (ICR). CD recurrence following surgery is common, although antibiotics can reduce short term recurrence rates. Following an ICR, it is unknown what happens to the fecal microbiota and how the microbiota relates to CD recurrence. To further investigate this, we analyzed fecal microbiomes of patients with CD (with and without an ICR) and compared to healthy controls. HYPOTHESIS Patients with CD and active inflammation have more dysbiosis of their fecal microbiomes, and ileocolonic resection (ICR) improves this dysbiosis. METHODS We performed a cross sectional study of fecal samples patients with CD (stratified by ICR status) and healthy controls. DNA was isolated and the V4 hypervariable region of the 16S rRNA gene was amplified and sequenced using the Illumina platform. Ecological metrics were applied to characterize fecal microbiomes. In our comparison, CD patients were further stratified based on their most recent colonoscopy into the following groups: 1) history of ICR versus surgically naïve CD patients, 2) active inflammation (in either the ileum and/or colon), and 3) active ileal inflammation versus none (colonic inflammation excluded). RESULTS Twenty-four CD patients (n=14, 58 % with ICR) and 38 healthy controls provided fecal samples. Global trends demonstrated that CD patients have significantly reduced richness (or observed taxonomic units) (Figure 1 A, p<0.0001) and significantly reduced Shannon diversity indices (Figure 1 B, p<0.0001) in their fecal microbiomes compared to healthy controls. Community diversity based on principal component analysis of Bray-Curtis pairwise dissimilarity indices is shows distinct clustering between healthy controls and CD patients (Figure 1 C). Richness and Shannon diversity index is not significantly different between CD patients that are surgically naïve compared with those that have undergone ICR (Figure 2 A and B). Richness and Shannon diversity indices are not significantly different between CD patients without versus with active inflammation (Figure 2 C and D) and is also not significant in CD patients without vs with ileal inflammation (Figure 2 E and F). CONCLUSION CD is characterized by fecal microbiota dysbiosis. ICR did not impact the fecal microbiota and fecal samples could not distinguish ileal inflammation. ICR paired with therapies to improve dysbiosis may affect CD recurrence.