P683 Patients with newly diagnosed fistulizing perianal Crohn's disease have a distinct microbial signature

Goren, I.(1);Ian, W.(2);Reshef, L.(3);Sharar Fischler, T.(1);Pauker, M.(1);Silverman, J.(4);Dotan, I.(1);Yanai, H.(1);

(1)Rabin Medical Center, Division of Gastroenterology, Petah Tikva, Israel;(2)Rabin Medical Center, Colorectal surgery- Department of surgery, Petah Tikva, Israel;(3)Tel Aviv University, Molecular microbiology and biotechnology, Tel Aviv, Israel;(4)Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv, Israel

Background

Alterations in gut bacterial microbiota are strongly associated with the pathogenesis of Crohn’s disease (CD). Up to 1/3 of patients with CD have perianal involvement (P-CD), either fistulizing (f-P-CD) or non-fistulizing (nf-P-CD). We hypothesized that alterations in fecal microbiota might drive perianal CD phenotypes.

Methods

Patients with newly diagnosed treatment naive CD were consecutively recruited. Patients were stratified into f-P-CD and nf-P-CD, and compared with CD without perianal involvement (non-P-CD).  Bacterial 16S rRNA gene sequencing was performed. Microbial dysbiosis index (MDI), Shannon diversity score (H) and log ratio between anaerobic and aerobic bacteria (anaerobic index, AI) were calculated. Linear discriminant analysis effect size (LEfSe) was used to identify specific taxa discriminating between different patient groups. Fecal calprotectin (FC) was measured.

Results

We included 97 CD patients (50 males, median age 28 [IQR 22-41] years). Other than perianal involvement patients in both groups had comparable distribution of CD location and phenotype. The microbial indices MDI, H and AI as well as FC levels, did not differ between the P-CD (n=25) and non-P-CD (n=72) groups. When compared to non-P-CD, the P-CD exhibited significantly lower relative abundance in the Streptococci genera (p=0.01) and in the Ruminiclostridium_5 genera (p=0.02). Within the P-CD group, patients with f-P-CD (n=12) had significantly lower H than those with nf-P-CD (means: 2.0 vs 2.45, p=0.045), while FC levels were comparable between f-P-CD and nf-P-CD. Moreover, proportions of Coprococcus_3 and Lacnoclostridium were reduced in patients with f-P-CD vs nf-P-CD (p= 0.008, p=0.05, respectively), while Streptococcus was elevated (p=0.03).

Conclusion

Perianal CD is a spectrum with distinct microbial alterations in different phenotypes. Microbial alterations correspond to the severity of perianal involvement. This finding may suggest that the microbiome has a mechanistic role in complicated perianal CD.