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OP022. Low microbial gene diversity and depletion of Akkermansia mucini-phila is associated with a relapsing course of ulcerative colitis

F. Casellas1, N. Borruel1, C. Manichanh1, E. Varela1, M. Antolín1, A. Torrejón1, V. Robles1, F. Guarner1, on behalf of MetaHIT Consortium1,2, 1Hospital Universitari Vall d'Hebron, Unitat Atenció Crohn-Colitis, Barcelona, Spain, 2MetaHIT Network, Partner Centres, Paris, France

Background

While the precise aetiology of ulcerative colitis (UC) is still unknown, a dysregulated immunologic response against gut bacteria appears to be the key event driving the inflammatory process that generates lesions. We followed UC patients from remission to disease relapse and analysed microbial communities in faecal samples by metagenomic sequencing.

Objective: To determine changes in faecal microbiota related with UC clinical course.

Methods

Faecal samples from 31 patients with clinically inactive UC and 30 first-degree relatives were obtained for whole-genome illumina sequencing of DNA extracts (cross-sectional study). Patients were followed for one-year or until relapse (CAI >4), samples and scores obtained every 2 months. To further explore findings, faecal samples from 106 UC patients were analysed by qPCR.

Results

Faecal microbial diversity (number of non-redundant microbial genes) was significantly reduced in UC during remission as compared to health. Moreover, reduced gene diversity was associated with past history of severe disease, since patients with one or more flares per year showed lower gene counts than patients with a milder clinical course (p < 0.05). Patients showed depletion of mucin degrading and butyrate producing species, including Akkermansia muciniphila (Akk), Lachnospiracea bacterium, Bacteroides xylano-solvens and Rumino-coccus bromii. Interestingly, Akk was not found in mucus obtained by rectal swabs (3 Akk positive in mucus out of 11 patients vs. 12 Akk positive out of 13 controls, p < 0.01). Patients on stable remission for one year did not show change in microbial diversity, but those suffering relapse showed a further reduction at beginning of relapse. Patients with Akk in faeces were more likely to be on stable remission. Presence of AKM in faeces was found to be predictive of one-year remission (positive predictive value: 84.6 [69–94]).

Conclusion

UC is associated with low microbial diversity, specifically with reduction of butyrate producing bacteria. Persistence of Akkermansia is related with better clinical outcome.