Are Helicobacter Pylori and Other Helicobacter Species Infection Associated with Human Biliary Lithiasis? A Meta-Analysis

Background

Since the isolation of Helicobacter species in biliary system, a hypothetical question was raised about the role of these agents in the development of cholelithiasis. This meta-analysis is to explore the association between the Helicobacter infection and biliary lithiasis.

Methodology/Principal Findings

A systematic literature search was performed to identify all eligible articles. Meta-analysis which was carried out using odds ratio and random effect model, 95% confidence intervals for odds ratio was calculated. Quantitative assessment of heterogeneity was explored by chi-square test with significance set at P value 0.10 and was measured using I ² statistic. Eighteen studies published between 1998 and 2011 were finally eligible for meta-analysis. H. Pylori, H. Bilis, H. Hepaticus, H. Pullorum and H. Ganmani were studied. With heterogeneity (I² = 69.5%, P<0.0001), significantly higher pooled infection rates of H. Pylori (OR: 2.59, 35.82% versus 26.75%, P = 0.01) and H. Hepaticus (OR: 3.13, 31.30% versus 12.12%, P = 0.02) were observed in lithiasis group. Higher prevalence of H. Pylori in cholelithiasis patients were reported by studies from East Asia, South Asia and South America. Evidences supporting the higher presence of H. Pylori in cholelithiasis patients could be found by PCR for detecting 16s rRNA in bile, 26kDa protein gene in biliary tissue and immunohistochemistry. Using multiple detection tests could increase the detection rate of H. Pylori.

Conclusions/Significances

Our meta-analysis suggests a trend of higher presence of H. Pylori in cholelithiasis patients than control group and this trend was significant in the regions with higher prevalence of this agent. Evidences supporting the association between Helicobacter and cholelithiasis could be found by using different tests but the gold standard for the identification of these bacteria in biliary system has yet to be established. Considering obvious heterogeneity, a large multi-center study will facilitate us to further clarify the association between the Helicobacter infection and cholelithiasis.     

幽门螺杆菌（Helicobacter pylori）研究进展

幽门螺杆菌（Ｈｅｌｉｃｏｂａｃｔｅｒｐｙｌｏｒｉ）研究进展常淑琴,苏华（黑龙江省卫生防疫站,哈尔滨）夏海华（黑龙江省科学院应用微生物研究所,哈尔滨）１９８３年Ｗａｒｒｔｅｎ和Ｍａｒｓｈａｌｌ报告,在活动性胃炎活检标本中,首次发现并培养成功一种螺旋型细...     

Is Helicobacter pylori a True Microaerophile?

BACKGROUND: There is no general consensus about the specific oxygen and carbon dioxide requirements of the human pathogen Helicobacter pylori. This bacterium is considered a microaerophile and consequently, it is grown under atmospheres at oxygen tensions 5-19% and carbon dioxide tensions 5-10%, both for clinical and basic and applied research purposes. The current study compared the growth of H. pylori in vitro, under various gas atmospheres, and determined some specific changes in the physiology of bacteria grown under different oxygen partial pressures. METHODS: Measurements of bacterial growth under various conditions were carried out employing classical solid and liquid culture techniques. Enzymatic activities were measured using spectrophotometric assays. RESULTS: H. pylori and all the other Helicobacter spp. tested had an absolute requirement for elevated carbon dioxide concentrations in the growth atmosphere. In contrast with other Helicobacter spp., H. pylori can tolerate elevated oxygen tensions when grown at high bacterial concentrations. Under 5% CO(2), the bacterium showed similar growth in liquid cultures under oxygen tensions from microaerobic (< 5%) to fully aerobic (21%) at cell densities higher than 5 x 10(5) cfu/ml for media supplemented with horse serum and 5 x 10(7) cfu/ml for media supplemented with beta-cyclodextrin. Evidence that changes occurred in the physiology of H. pylori was obtained by comparing the activities of ferredoxin:NADH (nicotinamide adenine dinucleotide) oxidoreductases of bacteria grown under microaerobic and aerobic atmospheres. CONCLUSIONS: H. pylori is a capnophile able to grow equally well in vitro under microaerobic or aerobic conditions at high bacterial concentrations, and behaved like oxygen-sensitive microaerophiles at low cell densities. Some characteristics of H. pylori cells grown in vitro under microaerobic conditions appeared to mimic better the physiology of organisms grown in their natural niche in the human stomach.     

Helicobacter pylori 26695 基因组尺度代谢研究进展

代谢网络在代谢功能研究、生物代谢过程控制、疾病诊断分析和药物靶标设计等方面具有重要理论和实践意义。生物信息学研究利用序列同源、结构模拟、对接等手段与生化实验有效结合促进了生物体代谢网络的进一步完善。本文作者在构建幽门螺杆菌（Helicobacter pylori 26695,H.pylori 26695）代谢网络的工作基础上综合了近年来研究者对H.pylori 26695代谢通路关键酶的研究成果,并结合基因组信息,综述了H.pylori 26695特异性的重要代谢通路。本文从基因组水平阐明代谢通路与基因的关系,并详细分析了关键酶对H.pylori 26695生理的重要作用,最后探讨了重构一个连续、完整的代谢网络面临的困难及其在药物靶标设计方面的研究前景。     

Could Helicobacter organisms cause inflammatory bowel disease?

The discovery of Helicobacter pylori sparked a revolution in the understanding and management of peptic ulcer disease and gastric cancer. Other Helicobacter species are recognized as important pathogenic agents in colitic diseases of rodents and primates, in particular Helicobacter bilis, Helicobacter fennelliae, Helicobacter hepaticus and Helicobacter trogontum. Helicobacter bilis and H. hepaticus are now routinely used to initiate rodent models of inflammatory bowel disease (IBD), particularly in immunocompromised hosts. Molecular evidence exists linking various non-pylori Helicobacter spp. with human IBD; however, attempts to culture organisms in this disease cohort have proved unsuccessful to date. Attributing causation has therefore proved elusive. Seven enterohepatic, non-pylori Helicobacter organisms have been successfully cultured from humans, namely Helicobacter canadensis, Helicobacter canis, Helicobacter cinaedi, H. fennelliae, Helicobacter pullorum, Helicobacter winghamensis and Helicobacter sp. flexispira taxon 8 (now classified as H. bilis). Of these, H. cinaedi and H. fennelliae are the closest to fulfilling Koch's postulates as causative agents in homosexual proctitis. The possibility that novel Helicobacter organisms have a role in the initiation of human IBD warrants further consideration and targeted investigations.     

Is Helicobacter pylori the cause of dyspepsia?

OBJECTIVE--To determine the association between infection with Helicobacter pylori and dyspepsia. DESIGN--Cross sectional study of dyspeptic subjects and age and sex matched controls identified by a questionnaire survey of all inhabitants aged 20-69. (Endoscopy, histological examination, and microbiological examinations of biopsies from the gastric mucosa were performed blind.) SETTING--Population based survey in Sørreisa, Norway. SUBJECTS--All 782 dyspeptic subjects (excluding those with a previous history of peptic ulcer, gall stones or kidney stones, and coronary heart disease) and controls were offered an endoscopy, of whom 309 dyspeptic subjects and 310 controls attended. MAIN OUTCOME MEASURES--Prevalences of endoscopic and histological diagnoses and of cultures positive for H pylori. RESULTS--A high prevalence of positive cultures, increasing with age, was found in both dyspeptic subjects (48%) and non-dyspeptic controls (36%) (p = 0.004). Positive cultures in both dyspeptic subjects and controls were strongly associated with histological gastritis (70%, 95% confidence interval 65.5 to 85.3; 60%, 52.7 to 67.7, respectively) and peptic ulcer (92%, 61.5 to 99.8; 64.1, 9.4 to 99.2, respectively). Only 3% of subjects with a histologically non-inflamed gastric mucosa had this infection (dyspeptic subjects 2%, 0.2 to 7.0; controls 4%; 1.2 to 8.8). CONCLUSIONS--The relation between dyspeptic symptoms and H pylori is dubious; H pylori seems to have a pathogenetic role in gastritis and may be a contributing factor but not a cause of peptic ulcer.     

幽门螺杆菌（Helicobacter pylori）的研究现状

(一)命名的过程1982年4月,Marshall等人在培养人体胃粘膜活组织解剖样品时,发现了一种螺旋状的细菌,由于它具有弯曲杆菌属(Campylobacter)的特征,被定名为Camplobacter pyloridis后发现该种名的加词在拉丁文语法上是错误的,因此更名为幽门弯曲杆菌(Campylobacter pylori)。     

Helicobacter pylori: an invading microorganism? A review

In this review we evaluate the pros and cons of Helicobacter pylori invasion of epithelial cells as part of the natural history of H. pylori infection. H. pylori is generally considered an extracellular microorganism. However, a growing body of evidence supports the controversial hypothesis that at least a subset of H. pylori microorganisms has an intracellular (intraepithelial) location. Most significant is the fact that H. pylori invades cultured epithelial cells with invasion frequencies similar to Yersinia enterocolitica and better than Shigella flexneri; furthermore, studies of invasion mechanisms suggest that H. pylori invasion of and survival within epithelial cells is not merely a passive event, but requires active participation of the microorganism. Although many studies of human gastric biopsy specimens have failed to demonstrate any intracellular H. pylori, some studies have revealed a minor fraction of H. pylori inside gastric epithelial cells, with possible linkage to peptic ulceration and epithelial cell damage. In conclusion, these data encourage further research to establish whether intracellular H. pylori does play a role in H. pylori colonization of the human stomach and in peptic ulcer pathogenesis.     

Does Helicobacter pylori cause gastric cancer via oxidative stress?

Epidemiologic evidence strongly supports a causal role for Helicobacter pylori in gastric carcinogenesis. The infection was recognized as a Class I human carcinogen by the International Agency for Research on Cancer in 1994. The bacterium does not induce carcinogenesis by itself. The present scientific consensus is that the bacterial oncogenic role is mediated by the chronic active inflammation it elicits in the gastric mucosa. Although the ultimate basic mechanism of carcinogenesis is unknown, strongly suggestive evidence points to oxidative stress as having a pivotal role in the process. This review discusses some of the evidence accumulated so far to support such a role. Numerous avenues of research are open and represent an intriguing challenge to the scientific community.     

Helicobacter pylori gastritis: a Th1 mediated disease?

Helicobacter pylori is now considered to be the main cause for most stomach diseases including ulcer, MALT lymphoma, adenocarcinoma and gastritis. The infection with this bacterium is chronic despite a local and systemic immune response towards it. Among the cellular infiltrate that arises during H. pylori-mediated gastritis, there is a considerable frequency of CD4+ Th1 cells producing IFNgamma, but not of Th2 cells producing IL-4. Since IFNgamma may induce binding of H. pylori to gastric epithelial cells followed by apoptosis of these cells, one may speculate that H. pylori-mediated diseases are in part autoimmune diseases initiated by H. pylori-specific Th1 cells infiltrating the gastric mucosa. Recent support for this hypothesis comes from an animal model in which mice are infected with H. pylori and display strongly reduced gastritis in the absence of IFNgamma.     

Enterohepatic Helicobacter in Ulcerative Colitis: Potential Pathogenic Entities?

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.