溃疡性结肠炎中的肠肝螺旋杆菌：潜在的致病实体？
Enterohepatic helicobacter in ulcerative colitis: potential pathogenic entities?
机构信息
Gastrointestinal Research Group, Division of Applied Medicine, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom.
出版信息
PLoS One. 2011 Feb 23;6(2):e17184. doi: 10.1371/journal.pone.0017184.
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.
背景
被称为“生态失调”的细菌种群变化被认为是溃疡性结肠炎（UC）发病机制的核心。特别是，新型幽门螺杆菌在人类 UC 中可能发挥作用的可能性一直存在争议，但尚未得到全面研究。本研究旨在开发一种分子方法来检测 UC 患者和非 UC 患者中是否存在幽门螺杆菌。
方法/主要发现：开发了一种双重分子方法来检测幽门螺杆菌。设计了针对属幽门螺杆菌的寡核苷酸探针，并与已发表的 H. pylori 探针的验证一起进行了优化。还对幽门螺杆菌属和 H. pylori PCR 引物进行了全面评估。在评估 UC 队列之前，该综合方法在一系列胃肠道样本中进行了评估。为 FISH 分析提供了 106 名个体的存档结肠样本（57 名 UC 和 49 名非 IBD 对照）。前瞻性收集了 118 名个体进行双重 FISH 和 PCR 分析（86 名 UC 和 32 名非 IBD 对照）。另外 27 名非 IBD 对照可用于 PCR 分析。所有幽门螺杆菌 PCR 阳性样本均进行测序。使用 Pearson Chi Squared 2 tailed 检验对幽门螺杆菌与每个研究组之间的关联进行统计学分析。UC 患者中幽门螺杆菌属 PCR 阳性率明显高于对照组（32/77 与 11/59，p=0.004）。序列分析表明，UC 组中肠肝幽门螺杆菌种的患病率明显高于对照组（30/77 与 2/59，p<0.0001）。74 名（67.9%）受试者的 PCR 和 FISH 结果一致。大多数不一致的结果归因于 FISH 的阳性率高于 PCR。
结论/意义：幽门螺杆菌值得考虑作为 UC 的潜在致病实体。需要从结肠组织中分离这些细菌，以便根据既定标准对其致病性进行研究。
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