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P410. Microbiota profiling in PSC and control patients: A pilot study

N. Rossen1, S. Fuentes2, K. Boonstra1, G. D'Haens1, H. Heilig2, E. Zoetendal2, W. de Vos2, C. Ponsioen1, 1Academic Medical Center, Gastroenterology & Hepatology, Amsterdam, Netherlands, 2Wageningen University, Laboratory of Microbiology, Wageningen, Netherlands

Background

Primary sclerosing cholangitis (PSC) is a cholestatic liver disease, strongly associated with a particular phenotype of inflammatory bowel disease (IBD) with right-sided colonic involvement. The aim of our study was to characterize the intestinal mucosal microbiota at the ileocecal level in PSC patients.

Methods

We included PSC patients, UC patients and non-inflammatory controls. The microbiota composition based the on 16S rRNA diversity was determined on pooled ileal-cecal biopsies per patient using the Human Intestinal Tract Chip (HITChip) (Rajilic-Stojanovic et al, Environ. Microbiol. 2009).

Results

We prospectively included 34 patients; 14 patients in the PSC group, 11 patients in the UC group and 9 non-inflammatory controls. In the PSC group, median age was 37.5 years (IQR 25–55), 86% of the patients were male, median PSC disease duration was 4.5 years (range 0–17) and 12 of these PSC patients (86%) had concomitant IBD; 4 Crohn's disease (CD) and 8 ulcerative colitis (UC). In the UC group, median age was 50 years (IQR 37–67) and 82% of the patients were male. In non-inflammatory controls, median age was 65 years (IQR 50–70) and 78% were male. Samples did not cluster by disease group. Similarity of the profiles within the PSC cohort was different compared to non-inflammatory controls (p = 0.03). At genus-like level, the relative abundance of Uncultered Clostridiales was lower in PSC (0.24±0.10%) compared to IBD (0.41±0.29%) and controls (0.49±0.25%) (False discovery rate: 0.038; p ≤ 0.001). No significant differences in diversity and evenness were found, but the richness differed across the groups and was lowest in the PSC patients: 685±181 in PSC, 746±210 in IBD and 821±175 in controls (p = 0.02).

Conclusion

The mucosal adherent microbiota at the ileocecal level in PSC patients shows significantly reduced richness. At genus-like level, the relative abundance of Uncultured Clostridiales is significantly lower as compared to IBD- and healthy controls. The reduced amounts of the Uncultured Clostridiales in PSC biopsies can be considered as an indication for a compromised gut as we have recently observed that this group of not yet cultured Firmicutes correlates significantly with health (Lahti et al, unpublished data).