Alteration of Intestinal Dysbiosis by Fecal Microbiota Transplantation Does not Induce Remission in Patients with Chronic Active Ulcerative Colitis

被引:246
作者
Kump, Patrizia K. [1 ]
Groechenig, Hans-Peter [2 ]
Lackner, Stefan [3 ]
Trajanoski, Slave [3 ]
Reicht, Gerhard [4 ]
Hoffmann, K. Martin [5 ]
Deutschmann, Andrea [5 ]
Wenzl, Heimo H. [1 ]
Petritsch, Wolfgang [1 ]
Krejs, Guenter J. [1 ]
Gorkiewicz, Gregor [6 ]
Hoegenauer, Christoph [1 ]
机构
[1] Med Univ Graz, Dept Internal Med, Div Gastroenterol & Hepatol, A-8036 Graz, Austria
[2] Barmherzige Bruder Hosp, Dept Internal Med, St Veit An Der Glan, Austria
[3] Med Univ Graz, Med Res Ctr, A-8036 Graz, Austria
[4] Barmherzige Bruder Hosp, Dept Internal Med, Graz, Austria
[5] Med Univ Graz, Dept Pediat, A-8036 Graz, Austria
[6] Med Univ Graz, Inst Pathol, A-8036 Graz, Austria
关键词
inflammatory bowel disease; ulcerative colitis; fecal microbiota transplantation; stool transplantation; intestinal microbiota; 16S rDNA; microbial community profiling; INFLAMMATORY-BOWEL-DISEASE; GUT MICROBIOTA; DIVERSITY; THERAPY; MUCOSA; MANAGEMENT;
D O I
10.1097/MIB.0b013e31829ea325
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background:In patients with ulcerative colitis (UC), alterations of the intestinal microbiota, termed dysbiosis, have been postulated to contribute to intestinal inflammation. Fecal microbiota transplantation (FMT) has been used as effective therapy for recurrent Clostridium difficile colitis also caused by dysbiosis. The aims of the present study were to investigate if patients with UC benefit from FMT and if dysbiosis can be reversed.Methods:Six patients with chronic active UC nonresponsive to standard medical therapy were treated with FMT by colonoscopic administration. Changes in the colonic microbiota were assessed by 16S rDNA-based microbial community profiling using high-throughput pyrosequencing from mucosal and stool samples.Results:All patients experienced short-term clinical improvement within the first 2 weeks after FMT. However, none of the patients achieved clinical remission. Microbiota profiling showed differences in the modification of the intestinal microbiota between individual patients after FMT. In 3 patients, the colonic microbiota changed toward the donor microbiota; however, this did not correlate with clinical response. On phylum level, there was a significant reduction of Proteobacteria and an increase in Bacteroidetes after FMT.Conclusions:FMT by a single colonoscopic donor stool application is not effective in inducing remission in chronic active therapy-refractory UC. Changes in the composition of the intestinal microbiota were significant and resulted in a partial improvement of UC-associated dysbiosis. The results suggest that dysbiosis in UC is at least in part a secondary phenomenon induced by inflammation and diarrhea rather than being causative for inflammation in this disease.
引用
收藏
页码:2155 / 2165
页数:11
相关论文
共 46 条
[21]   Autophagy, Microbial Sensing, Endoplasmic Reticulum Stress, and Epithelial Function in Inflammatory Bowel Disease [J].
Kaser, Arthur ;
Blumberg, Richard S. .
GASTROENTEROLOGY, 2011, 140 (06) :1738-U61
[22]   Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection in 26 Patients Methodology and Results [J].
Kelly, Colleen R. ;
de Leon, Lauren ;
Jasutkar, Niren .
JOURNAL OF CLINICAL GASTROENTEROLOGY, 2012, 46 (02) :145-149
[23]  
Kindt R., 2006, Tree diversity analysis: a manual and software for common statistical methods for ecological and biodiversity studies
[24]  
Kornbluth A, 2010, AM J GASTROENTEROL, V105, P501, DOI 10.1038/ajg.2009.727
[25]   Review article: faecal transplantation therapy for gastrointestinal disease [J].
Landy, J. ;
Al-Hassi, H. O. ;
McLaughlin, S. D. ;
Walker, A. W. ;
Ciclitira, P. J. ;
Nicholls, R. J. ;
Clark, S. K. ;
Hart, A. L. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2011, 34 (04) :409-415
[26]   Has the Microbiota Played a Critical Role in the Evolution of the Adaptive Immune System? [J].
Lee, Yun Kyung ;
Mazmanian, Sarkis K. .
SCIENCE, 2010, 330 (6012) :1768-1773
[27]   Twin Study Indicates Loss of Interaction Between Microbiota and Mucosa of Patients With Ulcerative Colitis [J].
Lepage, Patricia ;
Haesler, Robert ;
Spehlmann, Martina E. ;
Rehman, Ateequr ;
Zvirbliene, Aida ;
Begun, Alexander ;
Ott, Stephan ;
Kupcinskas, Limas ;
Dore, Joel ;
Raedler, Andreas ;
Schreiber, Stefan .
GASTROENTEROLOGY, 2011, 141 (01) :227-236
[28]   UniFrac: a new phylogenetic method for comparing microbial communities [J].
Lozupone, C ;
Knight, R .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2005, 71 (12) :8228-8235
[29]   The gut microbiota in IBD [J].
Manichanh, Chaysavanh ;
Borruel, Natalia ;
Casellas, Francesc ;
Guarner, Francisco .
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2012, 9 (10) :599-608
[30]   Reshaping the gut microbiome with bacterial transplantation and antibiotic intake [J].
Manichanh, Chaysavanh ;
Reeder, Jens ;
Gibert, Prudence ;
Varela, Encarna ;
Llopis, Marta ;
Antolin, Maria ;
Guigo, Roderic ;
Knight, Rob ;
Guarner, Francisco .
GENOME RESEARCH, 2010, 20 (10) :1411-1419