P-218 YI Increased Abundance of Colonic Mucosal Faecalibacterium Prausnitzii in Pediatric Treatment-Naive Ulcerative Colitis

Abstract

BACKGROUND: Ulcerative colitis (UC) pathogenesis likely involves a dysregulated interaction between host genes, intestinal microbes and environment. Twenty percent of UC presents in children, where the disease is usually more aggressive than in adults. In regards to the microbiome, Faecalibacterium prausnitzii has been observed to harbor anti-inflammatory properties, and has been associated both with Crohn's disease (CD) and UC. Lower abundance of F. prausnitzii has been detected in patients with ileal CD. The decreased abundance of this bacterium has been associated with an increased risk of post-surgical relapse in CD patients as well. In UC, conflicting observations have been made about F. prausnitzii abundance. One study connected lower abundance of F. prausnitzii with shorter time in remission and greater risk of UC flare. However, most of these metagenomic observations have limitations, such as restriction to adults, studying stool samples, and including treatment experienced patients. All of these factors may influence microbiome composition, and limited mucosa associated metagenomic data exists in respect to pediatric UC in untreated patients. However, such information is likely to carry important information towards unraveling the pathogenesis of this UC subtype. The aim of our study was to characterize the colonic mucosal microbiome of treatment- naive pediatric UC patients. METHODS: Left sided colonic biopsy samples from 9 treatment naive UC patients and 13 controls (no endoscopic or histologic evidence of UC) were studied. The Illumina MiSeq sequencing platform was used to interrogate the V1-V3 regions of the bacterial 16s rRNA gene. Processing of sequence data, assignment of operational taxonomic units (OTUs) and calculation of alpha-diversity were performed in QIIME (Quantitative Insights Into Microbial Ecology). STAMP (Statistical analysis of taxonomic and functional profiles) was used to analyze the high-throughput metagenomic data set. Clinical information, including Montreal classification of disease extent, physician's global assessment of severity and medications were reviewed. RESULTS: Pediatric UC patients had a comparable Shannon diversity index compared to controls. There were no significant differences between the groups when analyzed at the phylum, class, order, family, genus or species levels. There was, however, a trend towards a higher abundance of F. prausnitzii in UC patients compared to controls (P = 0.069). Significantly (Fischer exact test: P = 0.027) more UC patients (7/9 = 77.8%) had >3% F. prausnitzii abundance in the colonic mucosa than controls (3/13 = 23.1%). F. prausnitzii abundance at diagnosis did not predict short term (within 6 months) clinical outcomes in this small cohort. CONCLUSIONS: Our study demonstrated limited, but detectable differences between the colonic mucosal microbiome of treatment naive UC patients and controls in spite the small sample sizes. Significantly more UC patients had increased abundance of F. prausnitzii than controls. These results warrant further studies on larger groups to clarify the role of F. prausnitzii in pediatric UC.