Enterohepatic Helicobacter in ulcerative colitis

potential pathogenic entities?

John M Thomson, Richard Hansen, Susan H Berry, Mairi E Hope, Graeme I Murray, Indrani Mukhopadhya, Mairi H McLean, Zeli Shen, James G Fox, Emad El-Omar, Georgina L Hold

Research output: Contribution to journalArticle

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Abstract

Background
Changes in bacterial populations termed “dysbiosis” are thought central to ulcerative colitis (UC) pathogenesis. In particular, the possibility that novel Helicobacter organisms play a role in human UC has been debated but not comprehensively investigated. The aim of this study was to develop a molecular approach to investigate the presence of Helicobacter organisms in adults with and without UC.

Methodology/Principal Findings
A dual molecular approach to detect Helicobacter was developed. Oligonucleotide probes against the genus Helicobacter were designed and optimised alongside a validation of published H. pylori probes. A comprehensive evaluation of Helicobacter genus and H. pylori PCR primers was also undertaken. The combined approach was then assessed in a range of gastrointestinal samples prior to assessment of a UC cohort. Archival colonic samples were available from 106 individuals for FISH analysis (57 with UC and 49 non-IBD controls). A further 118 individuals were collected prospectively for dual FISH and PCR analysis (86 UC and 32 non-IBD controls). An additional 27 non-IBD controls were available for PCR analysis. All Helicobacter PCR-positive samples were sequenced. The association between Helicobacter and each study group was statistically analysed using the Pearson Chi Squared 2 tailed test. Helicobacter genus PCR positivity was significantly higher in UC than controls (32 of 77 versus 11 of 59, p = 0.004). Sequence analysis indicated enterohepatic Helicobacter species prevalence was significantly higher in the UC group compared to the control group (30 of 77 versus 2 of 59, p<0.0001). PCR and FISH results were concordant in 74 (67.9%) of subjects. The majority of discordant results were attributable to a higher positivity rate with FISH than PCR.

Conclusions/Significance
Helicobacter organisms warrant consideration as potential pathogenic entities in UC. Isolation of these organisms from colonic tissue is needed to enable interrogation of pathogenicity against established criteria.
Original languageEnglish
Article numbere17184
Number of pages9
JournalPloS ONE
Volume6
Issue number2
DOIs
Publication statusPublished - 23 Feb 2011

Fingerprint

Helicobacter
colitis
Ulcerative Colitis
Polymerase Chain Reaction
Helicobacter pylori
Pylorus
organisms
Oligonucleotide Probes
Dysbiosis
Tissue
oligonucleotide probes
sampling
Sequence Analysis
Virulence
pathogenicity
pathogenesis
sequence analysis
Control Groups

Keywords

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cohort Studies
  • Colitis, Ulcerative
  • Female
  • Helicobacter
  • Helicobacter Infections
  • Humans
  • Intestinal Mucosa
  • Intestines
  • Liver
  • Male
  • Microbiological Techniques
  • Middle Aged
  • Molecular Diagnostic Techniques
  • Validation Studies as Topic
  • Young Adult
  • Evaluation Studies
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Enterohepatic Helicobacter in ulcerative colitis : potential pathogenic entities? / Thomson, John M; Hansen, Richard; Berry, Susan H; Hope, Mairi E; Murray, Graeme I; Mukhopadhya, Indrani; McLean, Mairi H; Shen, Zeli; Fox, James G; El-Omar, Emad; Hold, Georgina L.

In: PloS ONE, Vol. 6, No. 2, e17184, 23.02.2011.

Research output: Contribution to journalArticle

Thomson, John M ; Hansen, Richard ; Berry, Susan H ; Hope, Mairi E ; Murray, Graeme I ; Mukhopadhya, Indrani ; McLean, Mairi H ; Shen, Zeli ; Fox, James G ; El-Omar, Emad ; Hold, Georgina L. / Enterohepatic Helicobacter in ulcerative colitis : potential pathogenic entities?. In: PloS ONE. 2011 ; Vol. 6, No. 2.
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abstract = "BackgroundChanges in bacterial populations termed “dysbiosis” are thought central to ulcerative colitis (UC) pathogenesis. In particular, the possibility that novel Helicobacter organisms play a role in human UC has been debated but not comprehensively investigated. The aim of this study was to develop a molecular approach to investigate the presence of Helicobacter organisms in adults with and without UC.Methodology/Principal FindingsA dual molecular approach to detect Helicobacter was developed. Oligonucleotide probes against the genus Helicobacter were designed and optimised alongside a validation of published H. pylori probes. A comprehensive evaluation of Helicobacter genus and H. pylori PCR primers was also undertaken. The combined approach was then assessed in a range of gastrointestinal samples prior to assessment of a UC cohort. Archival colonic samples were available from 106 individuals for FISH analysis (57 with UC and 49 non-IBD controls). A further 118 individuals were collected prospectively for dual FISH and PCR analysis (86 UC and 32 non-IBD controls). An additional 27 non-IBD controls were available for PCR analysis. All Helicobacter PCR-positive samples were sequenced. The association between Helicobacter and each study group was statistically analysed using the Pearson Chi Squared 2 tailed test. Helicobacter genus PCR positivity was significantly higher in UC than controls (32 of 77 versus 11 of 59, p = 0.004). Sequence analysis indicated enterohepatic Helicobacter species prevalence was significantly higher in the UC group compared to the control group (30 of 77 versus 2 of 59, p<0.0001). PCR and FISH results were concordant in 74 (67.9{\%}) of subjects. The majority of discordant results were attributable to a higher positivity rate with FISH than PCR.Conclusions/SignificanceHelicobacter organisms warrant consideration as potential pathogenic entities in UC. Isolation of these organisms from colonic tissue is needed to enable interrogation of pathogenicity against established criteria.",
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AU - Thomson, John M

AU - Hansen, Richard

AU - Berry, Susan H

AU - Hope, Mairi E

AU - Murray, Graeme I

AU - Mukhopadhya, Indrani

AU - McLean, Mairi H

AU - Shen, Zeli

AU - Fox, James G

AU - El-Omar, Emad

AU - Hold, Georgina L

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N2 - BackgroundChanges in bacterial populations termed “dysbiosis” are thought central to ulcerative colitis (UC) pathogenesis. In particular, the possibility that novel Helicobacter organisms play a role in human UC has been debated but not comprehensively investigated. The aim of this study was to develop a molecular approach to investigate the presence of Helicobacter organisms in adults with and without UC.Methodology/Principal FindingsA dual molecular approach to detect Helicobacter was developed. Oligonucleotide probes against the genus Helicobacter were designed and optimised alongside a validation of published H. pylori probes. A comprehensive evaluation of Helicobacter genus and H. pylori PCR primers was also undertaken. The combined approach was then assessed in a range of gastrointestinal samples prior to assessment of a UC cohort. Archival colonic samples were available from 106 individuals for FISH analysis (57 with UC and 49 non-IBD controls). A further 118 individuals were collected prospectively for dual FISH and PCR analysis (86 UC and 32 non-IBD controls). An additional 27 non-IBD controls were available for PCR analysis. All Helicobacter PCR-positive samples were sequenced. The association between Helicobacter and each study group was statistically analysed using the Pearson Chi Squared 2 tailed test. Helicobacter genus PCR positivity was significantly higher in UC than controls (32 of 77 versus 11 of 59, p = 0.004). Sequence analysis indicated enterohepatic Helicobacter species prevalence was significantly higher in the UC group compared to the control group (30 of 77 versus 2 of 59, p<0.0001). PCR and FISH results were concordant in 74 (67.9%) of subjects. The majority of discordant results were attributable to a higher positivity rate with FISH than PCR.Conclusions/SignificanceHelicobacter organisms warrant consideration as potential pathogenic entities in UC. Isolation of these organisms from colonic tissue is needed to enable interrogation of pathogenicity against established criteria.

AB - BackgroundChanges in bacterial populations termed “dysbiosis” are thought central to ulcerative colitis (UC) pathogenesis. In particular, the possibility that novel Helicobacter organisms play a role in human UC has been debated but not comprehensively investigated. The aim of this study was to develop a molecular approach to investigate the presence of Helicobacter organisms in adults with and without UC.Methodology/Principal FindingsA dual molecular approach to detect Helicobacter was developed. Oligonucleotide probes against the genus Helicobacter were designed and optimised alongside a validation of published H. pylori probes. A comprehensive evaluation of Helicobacter genus and H. pylori PCR primers was also undertaken. The combined approach was then assessed in a range of gastrointestinal samples prior to assessment of a UC cohort. Archival colonic samples were available from 106 individuals for FISH analysis (57 with UC and 49 non-IBD controls). A further 118 individuals were collected prospectively for dual FISH and PCR analysis (86 UC and 32 non-IBD controls). An additional 27 non-IBD controls were available for PCR analysis. All Helicobacter PCR-positive samples were sequenced. The association between Helicobacter and each study group was statistically analysed using the Pearson Chi Squared 2 tailed test. Helicobacter genus PCR positivity was significantly higher in UC than controls (32 of 77 versus 11 of 59, p = 0.004). Sequence analysis indicated enterohepatic Helicobacter species prevalence was significantly higher in the UC group compared to the control group (30 of 77 versus 2 of 59, p<0.0001). PCR and FISH results were concordant in 74 (67.9%) of subjects. The majority of discordant results were attributable to a higher positivity rate with FISH than PCR.Conclusions/SignificanceHelicobacter organisms warrant consideration as potential pathogenic entities in UC. Isolation of these organisms from colonic tissue is needed to enable interrogation of pathogenicity against established criteria.

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