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/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.
Highlights
Ulcerative colitis (UC) is a chronic condition of the human colon which affects the superficial mucosal layer from the rectum and extending proximally for variable distances [1]
Changes in bacterial populations to the detriment of the host have been termed ‘‘dysbiosis’’ and this change is thought central to inflammatory bowel disease (IBD) pathogenesis
The same 50 samples tested positive by PCR for Helicobacteraceae, H. pylori specific and universal bacterial primer sets with a subset of results (N = 10) subjected to sequence analysis which confirmed the presence of H. pylori
Summary
Ulcerative colitis (UC) is a chronic condition of the human colon which affects the superficial mucosal layer from the rectum and extending proximally for variable distances [1] This variable phenotype remains a puzzle, as does our difficulty in achieving long-term cure with current treatments. The possibility of infection as a trigger event for, or as the cause of, inflammatory bowel disease (IBD) has long been debated with various organisms being suggested as pathogens. None of these organisms have been conclusively proven as causative agents.
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