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P455. Improvement of ulcerative-colitis-associated microbiota dysbiosis after treatment with mesalazine-MMX (Mezavant®) using mucosal Faecalobacterium prausnitzii/Escherichia coli index as a marker

J.O. Miquel Cusachs1, D. Busquets Casals2, M. Serra-Pages1,3, J. Garcia-Gil4, X. Aldeguer Manté1, 1Hospital universitari de Girona, Dr Trueta, Gastroenterology, Girona, Spain, 2Hospital Universitari de Girona, Gastroenterology. IBD unit, Girona, Spain, 3IDiBGi, Gastroenterology. IBD unit, Girona, Spain, 4Universitat de Girona, Biology, Girona, Spain

Background

Microbiota (MI) in Crohn's disease's (CD) and ulcerative colitis (UC) are structurally different from healthy ones. We assume that the inflammation on colon mucosa may disrupt the normal MI ecosystem. Thus, any treatment given to curb the inflammation process has to be expressed by a recovery of the lost healthy equilibrium. In this study, our research group has developed a bacterial marker to evaluate treatment effectiveness on UC. We designed a specific index of Fp/Ec (FEI), based on the disappearance of Faecali-bacterium prausnitzii (Fp) and the different abundance of E. coli (Ec). In previous studies, it has been established that the lower the value the more disturbed is the MI ecosystem.

We designed a study to assess mesalazine-MMX (MZX) clinical response on mild/moderate UC and how that correlates on MI dysbiosis changes by examining FEI, previous (T0) and after (T1) treatment (TM).

Methods

We obtained rectal biopsy from mild/moderate UC patients on MZX (4.8 g once daily) given with intention to treat and re-sample them 4 wks after. We included 8 patients in total. Biopsies are obtained from first 5 cm of rectum by flexible gastroscope with standard procedures.

Inclusion criteria were: Patient >18yo. UC diagnosed histologically, naïve to TM, with a mild/moderate flare (Mayo index below 5) and histological criteria; and signed informed consent. We excluded patients with previous antibiotic and/or any concomitant drugs aimed to IBD TM given in the previous 6 months. All samples were analyzed using DNA real-time PCR methods.

Results

All patients but one in this study showed an improvement on disease activity as measured by Mayo Index. At T0, patients showed an FEI under 2.6 (previously established cut-off point, COP, for major dysbiosis) and in T1 the median was 3,150. That increase on value is related to the improvement on MI dysbiosis. In T1, the number of EC was reduced (in average 55%) of patients. There were no differences in the total number of Fp after TM. MZX is able to significantly (p = 0.039) change the FEI above the COP. The FEI detects, with 83% of accuracy, the MI dysbiosis improvement. Coefficient of variation after TM of the FEI is 0.34%.

Conclusion

TM on mild/moderate UC flare with MZX contributes to an improvement on dysbiosis situation as shown by a clear increase in the FEI. FEI looks as a good marker to measure MI dysbiosis and thus, it is a promising new tool to assess response to TM on UC.

This study has been supported by Shire, Inc.