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P364. Successful improvement of dysbiosis by fecal microbiota transplantation is not sufficient to induce clinical remission in chronic active ulcerative colitis

P.K. Kump1, H.-P. Gröchenig2, S. Lackner3, S. Trajanovski3, G. Reicht4, K.M. Hoffmann5, H.H. Wenzl1, W. Petritsch1, G. Gorkiewicz6, C. Hoegenauer1, 1Medical University Graz, Gastroenterology and Hepatology, Graz, Austria, 2BHB Graz, Internal Medicine, St. Veith, Austria, 3Medical University Graz, Center of Medical Research, Graz, Austria, 4BHB Graz, Internal Medicine, Graz, Austria, 5University Hospital for Pediatric Diseases, Graz, Austria, 6University Graz, Institute of Pathology, Graz, Austria

Background

There is growing evidence, that dysbiosis has a pivotal role in the pathogenesis of ulcerative colitis (UC). Beside reduced bacterial richness of the intestinal microbiota, an increase of proteobacteria with proinflammatory effects has been described. Fecal microbiota transplantation (FMT), also known as fecal bacteriotherapy, is a new therapeutic approach to restore an altered intestinal microbiota. The aims of this study were to assess the efficacy as well as changes in the intestinal microbiome after FMT in chronic active UC.

Methods

Six patients with chronic, active, therapy-refractory UC, who were considered for total colectomy, were treated with FMT. Donor stool was applied as a single application during colonoscopy to the terminal ileum. Endoscopic and clinical follow up was performed at 4 different time points (day 1, 7, 30 and 90) within 3 month. Microbiota analyses of stool and mucosa samples were performed by 16S rDNA-based microbial community profiling using high-throughput pyrosequencing.

Results

Within the first 14 days all patients experienced a reduction of stool frequency, while microbiota analysis revealed a simultaneous transient increase of microbial richness. However, none of the 6 patients achieved a complete remission and only 2 of the 6 patients had a durable improvement in their clinical UC scores. Subsequently two patients underwent total colectomy and one additional patient was treated with cyclosporine A. Overall no serious side effects occurred and only one patient had a self-limiting episode of fever after FMT.

Microbiome profiling showed different patterns of microbiota remodelling either in terms of approaching to the donors' microbiota, creating a de novo microbial pattern, or by returning to the patient's baseline microbiome. Within the first week after FMT, bacterial richness increased on mucosal samples but decreased again thereafter. On phylum level, FMT significantly reduced over-represented proteobacteria, mainly of the enterobacteriaceae family and resulted in an increase of bacteroidetes.

Conclusion

Although FMT performed by a single colonoscopic application successfully reversed some features of dysbiosis in chronic active UC, it is not effective in inducing sustained remission in these patients. These findings suggest that dysbiosis is at least in part consequence and not cause of this disease.