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P671. Effects of isotretinoin treatment on murine gut microbiota composition

E. Becker1, C. Stanzel1, S. Schmidt2, K. Atrott1, L. Biedermann1, A. Rehman3, D. Jonas3, C. von Mering2, G. Rogler1, I. Frey-Wagner1, 1University Hospital Zurich, Gastroenterology & Hepatology, Zurich, Switzerland, 2University of Zurich, Molecular Life Sciences, Zurich, Switzerland, 3University Medical Center, Environmental Health Sciences, Freiburg, Germany

Background

In-vitro and in-vivo data have shown that retinoid treatment promotes an anti-inflammatory milieu with few adverse effects towards the gastrointestinal (GI) tract, yet there is current debate about a causal relation between retinoid treatment and inflammatory bowel disease (IBD). Patients have claimed that they developed acute intestinal inflammation during isotretinoin treatment or to develop inflammatory bowel disease (IBD) weeks or even years after cessation of the medication. We have previously shown that isotretinoin treatment has no adverse effects in two mouse models of inflammatory bowel disease [1]. Since the gut microbiota can metabolize retinoids, we investigated whether administration of retinoids might change the gut microbiota composition in a way that is favorable for the development of IBD.

Methods

Balb/c mice were treated with isotretinoin (30 mg/kg bodyweight) or vehicle orally for 2 weeks and kept for further 4 weeks to study potential direct and long-term effects. Fecal samples were collected before treatment, directly after the treatment period and four weeks later for analysis of gut microbiota composition by 16S rRNA gene sequencing on the GS-Flx 454 platform. Sequencing data were analyzed with the software QIIME to determine OTUs, calculate the relative abundance for each group and time point and to general principal coordinate analysis plots.

Results

Principle coordinate analysis showed no formation of clusters neither depending on treatment nor on time point of investigation indicating no fundamental differences between the gut microbiota composition of isotretinoin or vehicle treated animals or between the different time points studied. Some differences with regard to alpha and beta diversity between the different treatment groups as well as between the different time points studied were observed and are currently under further investigation.

Conclusion

Preliminary results with QIIME showed no substantial differences between isotretinoin and vehicle treated animals indicating that isotretinoin treatment had no fundamental effect on the composition of the murine gut microbiota. We are currently investigating the variations in alpha and beta diversity that were observed between groups exposed to isotretinoin and vehicle, as well as between the different time points.

1. Frey-Wagner I., (2013), Effects of retinoids in mouse models of colitis: benefit or danger to the gastrointestinal tract?