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P829 Mucosal 5-ASA concentration is associated with changes in mucosal bacterial microbiome diversity and composition in patients with quiescent ulcerative colitis

M. Olaisen*1,2,3, O. Spigset1,4, W. R. Brede4, A. Flatberg1, A. v1, B. Granlund1,2,5, E. S. Røyset1,6, A. K. Sandvik1,2,3,5, T. C. Martinsen1,3, R. Fossmark1,2,3

1Norwegian University of Science and Technology (NTNU), Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Trondheim, Norway, 2Liaison Committee between the Central Norway Regional Health Authority (RHA) and NTNU, Trondheim, Norway, 3St. Olav’s Hospital, Trondheim University Hospital, Department of Gastroenterology and Hepatology, Trondheim, Norway, 4St. Olav’s Hospital, Trondheim University Hospital, Department of Clinical Pharmacology, Trondheim, Norway, 5Norwegian University of Science and Technology (NTNU), Centre of Molecular Inflammation Research, Trondheim, Norway, 6St. Olav’s Hospital, Trondheim University Hospital, Department of Pathology, Trondheim, Norway

Background

5-aminosalicylic acid (5-ASA) is the mainstay of ulcerative colitis (UC) treatment and acts locally in the colonic mucosa by a variety of purposed mechanisms. Recent in vitro studies suggest that 5-ASA may affect intestinal bacteria’s ability to adhere to and infiltrate to the intestinal mucosa, which may be important in the pathogenesis of UC.

Methods

Mucosal 5-ASA concentration and bacterial microbiome in colon biopsies and faeces were analysed in patients with quiescent UC using mesalazine monotherapy 4.0–4.8 g/day. 5-ASA concentrations were measured in mucosal biopsies (sampled 10, 25 and 40 cm from the anal verge) by ultra-high-performance liquid chromatography. Bacterial microbiome was sequenced from one faecal sample and one biopsy sample (taken 25 cm from the anal verge) by 16S rRNA sequencing on Illumina MiSeq platform. Disease activity was assessed with Mayo score, Geboes histological score and faecal calprotectin. Regression analyses were performed to relate 5-ASA concentrations to bacterial abundances.

Results

Forty-two patients with UC were included. The disease activity was low with a median (IQR) total Mayo score of 1.0 (2.0), Geboes score of 1.1 (1.1) and a calprotectin concentration of 66 (211) mg/kg. Geometric mean (95% CI) 5-ASA mucosal concentration was 1.43 ng/mg (0.84–2.44). Mucosal 5-ASA concentration was positively associated with mucosal bacterial diversity (p = 0.0005), but not with faecal bacterial diversity (p = 0.66). The mucosal 5-ASA concentration was significantly associated with mucosal bacterial abundance on all taxonomic levels; high 5-ASA concentrations were associated with reduced abundance of Proteobacteria (p = 1.2·10–15) and increased abundance of Firmicutes (2.6·10–6) and Bacteroidetes (p = 3.1·10–4) on phylum-level. Furthermore, mucosal 5-ASA concentration was associated with abundances of 16 bacterial families and 19 bacterial genera; positive associations between mucosal 5-ASA concentration and Lachnospiraceae and Ruminococcaceae families, Faecalibacterium, Roseburia and Bifidobacterium genera and F. prausnitzii species were found. Mucosal 5-ASA concentration was negatively associated with the faecal abundance of Prevotella and Sutterella genera, for the former the association was also seen on family, order and class level. Mucosal 5-ASA concentration was not associated with disease activity.

Conclusion

For the first time, we demonstrate that a high mucosal 5-ASA concentration is associated with high mucosal bacterial diversity and a mucosal bacterial composition which is perceived favourable in UC. 5-ASA may have beneficial effects on the mucosal microbiome, which in turn may affect disease course.