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PMID: 21621540 Published · ppublish English Journal Article Multicenter Study Research Support, Non-U.S. Gov't Twin Study

Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis.

Gastroenterology ·Vol. 141 ·No. 1 ·2011-07-00 ·Pages 227-36

Lepage P, Häsler R, Spehlmann ME, Rehman A, Zvirbliene A, Begun A, Ott S, Kupcinskas L, Doré J, Raedler A, Schreiber S

Abstract

Interactions between genetic and environmental factors are believed to be involved in onset and initiation of inflammatory bowel disease. We analyzed the interaction between gastrointestinal mucosal microbiota and host genes in twin pairs discordant for ulcerative colitis (UC) to study the functional interaction between microbiota and mucosal epithelium. Biopsy were collected from sigmoid colon of UC patients and their healthy twins (discordant twin pairs) and from twins without UC. Microbiota profiles were determined from analysis of 16S ribosomal DNA libraries; messenger RNA profiles were determined by microarray analysis. Patients with UC had dysbiotic microbiota, characterized by less bacterial diversity and more Actinobacteria and Proteobacteria than that of their healthy siblings; healthy siblings from discordant twins had more bacteria from the Lachnospiraceae and Ruminococcaceae families than twins who were both healthy. In twins who were both healthy, 34 mucosal transcripts correlated with bacterial genera, whereas only 25 and 11 correlated with bacteria genera in healthy individuals and their twins with UC, respectively. Transcripts related to oxidative and immune responses were differentially expressed between patients with UC and their healthy twins. The transcriptional profile of the mucosa appears to interact with the colonic microbiota; this interaction appears to be lost in colon of patients with UC. Bacterial functions, such as butyrate production, might affect mucosal gene expression. Patients with UC had different gene expression profiles and lower levels of biodiversity than their healthy twins, as well as unusual aerobic bacteria. Patients with UC had lower percentages of potentially protective bacterial species than their healthy twins.

MeSH Terms
Adolescent Adult Bacteria/classification,genetics,growth & development Biopsy Case-Control Studies Cluster Analysis Colitis, Ulcerative/genetics,microbiology Colon, Sigmoid/microbiology DNA, Bacterial/isolation & purification Female Gene Expression Profiling Gene Expression Regulation Germany Heredity Host-Pathogen Interactions/genetics Humans Intestinal Mucosa/microbiology Lithuania Male Middle Aged Molecular Sequence Data Principal Component Analysis RNA, Ribosomal, 16S/genetics Ribotyping Twins, Dizygotic/genetics Twins, Monozygotic/genetics Young Adult
Chemicals
DNA, Bacterial RNA, Ribosomal, 16S
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Lepage Patricia
Institute of Clinical Molecular Biology, Christian-Albrechts University-Kiel, Kiel, Germany.
Häsler Robert
Spehlmann Martina E
Rehman Ateequr
Zvirbliene Aida
Begun Alexander
Ott Stephan
Kupcinskas Limas
Doré Joël
Raedler Andreas
Schreiber Stefan
Article Info
Journal
Gastroenterology
Abbr.
Gastroenterology
ISSN
1528-0012
Published
2011-07-00
Epub
2011-00-16
Pages
227-36
Language
English
Region
United States
NLM ID
0374630
Subset
IM
Databases
GENBANK
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