1. 枯草芽孢杆菌表面幽门螺杆菌尿素酶B的表达研究
J Med Microbiol. 2014 Oct 29. pii: jmm.0.076430-0. doi: 10.1099/jmm.0.076430-0.
Expression of Helicobacter pylori urease B on the surface of Bacillus subtilis spores.
Zhou Z1, Gong S2, Li X3, Yang Y2, Guan R2, Zhou S2, Yao S2, Xie Y2, Ou Z2, Zhao J2, Liu Z4.
幽门螺杆菌是慢性胃炎，消化道溃疡，胃腺癌及淋巴瘤的主要危险因素。由于临床工作中根除幽门螺杆菌药物疗效下降，幽门螺杆菌的疫苗研发重新获得人们的重视。枯草芽孢杆菌具有非致病性及产生芽孢的特点，孢子在极端条件下可存活，从而是将异源抗体抗原传送到诸如消化道这样的极端环境的理想载体。 本研究中，我们采用孢子外壳蛋白CotC作为融合伴侣在枯草芽孢杆菌孢子外壳表达幽门螺杆菌尿素酶B。Western印迹分析验证孢子的尿素酶B表达情况。表达尿素酶B抗原的重组孢子用于口服免疫，在小鼠体内产生了体液免疫反应。口服给药2周后，其粪便尿素酶B特异性分泌型IgA和血清IgG抗体水平显著增高。此外，重组尿素酶B孢子的口服免疫（0.25±0.13×106CFU）与非重组孢子治疗组（0.3×1.56±106CFU，P＜0.01）相比可显著减少胃内细菌负荷（84%）。这份报告显示，枯草芽孢杆菌表达的尿素酶B具有免疫原性且口服尿素酶B孢子可预防幽门螺杆菌感染。
译者点评：通过使枯草芽孢杆菌表达尿素酶获得幽门螺杆菌疫苗的方法具有一定的研究前景。
Abstract
Helicobacter pylori infection is a major risk factor for chronic gastritis, digestive ulcers, gastric adenocarcinoma and lymphoma. Due to the decreasing efficacy of anti-Helicobacter pylori antibiotic therapy in clinical practice, there is renewed interest in the development of anti-Helicobacter pylori vaccines. Bacillus subtilis is nonpathogenic and can produce endospores, which can survive under extreme conditions. These features make the Bacillus subtilis spore an ideal vehicle for delivery of heterologous antigens to extreme environments such as the gastrointestinal tract. In this study, we displayed Helicobacter pylori urease B protein on the Bacillus subtilis spore coat using spore coat protein CotC as a fusion partner. Western blotting analyses were used to verify urease B surface expression on spores. Recombinant spores displaying the urease B antigen were used for oral immunization and were shown to generate humoral response in mice. Urease B-specific secretory IgA in feces and IgG in serum reached significant levels 2 weeks after oral dosing. In addition, oral immunization of recombinant urease B spores induced a significant reduction (84%) in the stomach bacterial load (0.25±0.13 x 106CFU) compared to that in non-recombinant spores treated group (1.56±0.3 x 106CFU, P < 0.01). This report shows that urease B expressed on Bacillus subtilis spores was immunogenic and oral administration of urease B spores can provide protection against Helicobacter pylori infection.
2. 病例对照研究：幽门螺杆菌感染、非甾体类抗炎药、小剂量阿司匹林、抗高血压药物引起消化性溃疡出血的风险
J Gastroenterol Hepatol. 2014 Oct 22. doi: 10.1111/jgh.12805. [Epub ahead of print]
Risk of peptic ulcer bleeding associated with Helicobacter pylori infection, NSAIDs, low-dose aspirin, and antihypertensive drugs: A case-control study.
Nagata N1, Niikura R, Sekine K, Sakurai T, Shimbo T, Kishida Y, Tanaka S, Aoki T, Okubo H, Watanabe K, Yokoi C,Akiyama J, Yanase M, Mizokami M, Uemura N.
背景：
在幽门螺杆菌感染率高的亚洲地区，仍不明确抗凝或抗高血压药物等是否为消化性溃疡出血的危险因素。本研究旨在评估抗血栓形成的药物、血管紧张素II受体拮抗剂、血管紧张素转换酶(ACE)抑制剂、钙通道阻滞剂、α受体阻断剂、β受体阻断剂引起消化性溃疡出血风险。
方法:
这是一项前瞻性的病例对照研究。包括230例经内镜证实的消化性溃疡出血患者和920例内镜下未见出血的年龄和性别匹配的对照组患者（1:4）。调整后的消化性溃疡出血风险的比值比（AOR）由条件逻辑回归分析确定。
结果：
多变量分析显示，饮酒(AOR, 2.2; p<0.001)、消化性溃疡史(AOR, 4.8; p<0.001)、幽门螺杆菌感染史(AOR, 2.1; P<0.001)、合并症指数（AOR，1.1；P = 0.089）、非甾体类抗炎药（NSAIDs）（AOR，2.0；P = 0）和低剂量阿司匹林（AOR，P = 0.003）增加消化性溃疡出血风险；而根除幽门螺杆菌（AOR，0.03；P＜0.001）质子泵抑制剂（PPIs）（AOR，0.1；P＜0.001）和组胺2受体拮抗剂（H2RA）（AOR，0.1，P＜0.001）则降低消化性溃疡出血风险。幽门螺杆菌感染与NSAIDs药物间无显著相互作用（P = 0.913）。ARBs（P = 0.564）、ACE抑制剂（P = 0.213）、钙通道阻滞剂（P = 0.215）、α-阻滞剂（P = 0.810）和β-阻滞剂（P = 0.864）与消化性溃疡出血无关。
结论：
我们发现饮酒、消化性溃疡史、幽门螺杆菌感染史、NSAIDs药物应用史及低剂量阿司匹林应用史是消化性溃疡出血的独立危险因素。幽门螺杆菌感染与NSAIDs药物间未观察到显著相互作用。抗高血压药与消化性溃疡出血无关。
译者点评：饮酒、消化性溃疡史、幽门螺杆菌感染、NSAIDs及阿司匹林应用史是消化性溃疡出血的独立危险因素
Abstract
BACKGROUND:
The associations between antithrombotic or antihypertensive drugs and peptic ulcer bleeding (PUB) remain unknown, particularly in Asia, where Helicobacter pylori infection is prevalent. This study aims to evaluate the risks of PUB from antithrombotic drugs, angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, α-blockers, and β-blockers.
METHODS:
This prospective hospital-based case-control study included 230 patients with endoscopically verified PUB and 920 age- and sex-matched controls (1:4) without bleeding on screening endoscopy. Adjusted odds ratios (AOR) for the risk of PUB were determined by conditional logistic regression analysis.
RESULTS:
In multivariate analysis, alcohol consumption (AOR, 2.2; p<0.001), history of peptic ulcer (AOR, 4.8; p<0.001), H. pylori infection (AOR, 2.1; P<0.001), comorbidity index (AOR, 1.1; p=0.089), non-steroidal anti-inflammatory drugs (NSAIDs) (AOR, 2.0; P=0.025) and low-dose aspirin (AOR, 2.8; P=0.003) increased the risk of PUB, whereas H. pylori-eradication (AOR, 0.03; P<0.001), proton pump inhibitors (PPIs) (AOR, 0.1; P<0.001) and histamine 2-receptor antagonists (H2RA) (AOR, 0.1; P<0.001) reduced it. No significant interactions were observed between H. pylori infection and NSAIDs use for PUB (P=0.913). ARBs (P=0.564), ACE inhibitors (P=0.213), calcium channel blockers (P=0.215), α-blockers (P=0.810), and β-blockers (P=0.864) were not associated with PUB.
CONCLUSIONS:
We found that alcohol consumption, history of peptic ulcer, H. pylori infection, NSAIDs use, and low-dose aspirin use were independent risk factors for PUB, whereas H. pylori-eradication, PPIs use, and H2RA use reduced its risk. Interactions between H. pylori and NSAIDs use in PUB were not observed. No antihypertensive drug was associated with PUB.
3. 对日本儿童和青少年的发炎牙髓标本进行幽门螺杆菌DNA的检测
J Med Microbiol. 2014 Oct 20. pii: jmm.0.079491-0. doi: 10.1099/jmm.0.079491-0. [Epub ahead of print]
Detection of Helicobacter pylori DNA in inflamed dental pulp specimens from Japanese children and adolescents.
Ogaya Y1, Nomura R2, Watanabe Y3, Nakano K1.
口腔的幽门螺杆菌定植被人为是儿童期HP感染的一个传播途径。已有很多研究报道利用不同PCR方法检测口腔标本中幽门螺杆菌的DNA，其检出率亦不同。这些检出率的差异使口腔幽门螺杆菌感染率的评估变得复杂。在该研究中，研究者构建了一个新的PCR幽门螺杆菌检测系统，并用它来分析口腔标本。首先，研究者参照GenBank数据库中登记的48株幽门螺杆菌株的全基因组信息对常用于幽门螺杆菌检测的基因核苷酸序列进行比较。选择扩增为约为300-400 bp的片段作为候选引物组，使用每个引物组对检测系统的特异性和敏感性进行评价。选出合适的靶向尿素的五组引物，其中一个单一引物组包含在PCR体系内。系统的灵敏度合适且将每反应1-10个细胞定为检测极限。这种新的PCR系统是用来检查收集自日本儿童，青少年和年轻成年人的口腔标本的幽门螺杆菌的分布（40个发炎的牙髓组织，40份唾液样本）。PCR分析表明，在发炎的牙髓组织幽门螺杆菌的检测率是15%，而所有唾液标本中均无阳性发现。我们的新的PCR系统是检测幽门螺杆菌的可靠工具。结果显示在牙髓标本中可以检测到HP，而在唾液中为阴性。提示牙髓的根管可能是幽门螺杆菌贮存的场所。
译者点评：本文作者提出了检测牙髓中幽门螺杆菌的一种新的PCR系统。但由于PCR方法本身的局限，如何看待检测结果尚需商榷。
Abstract
The oral cavity has been implicated as a source of Helicobacter pylori infection in childhood. Various PCR methods have been used to detect H. pylori DNA in oral specimens with various detection rates reported. Such disparity in detection rates complicates the estimation of the true infectious rate of H. pylori in the oral cavity. In the present study, we constructed a novel PCR system for H. pylori detection and used it to analyze oral specimens. Firstly, the nucleotide alignments of genes commonly used for H. pylori detection were compared using complete genome information for 48 strains registered in the GenBank database. Candidate primer sets with an estimated amplification size of approximately 300-400 bp were selected, and the specificity and sensitivity of the detection system using each primer set evaluated. Five sets of primers targeting urea were considered appropriate, of which a single primer set was chosen for inclusion in the PCR system. The sensitivity of the system was considered appropriate and its detection limit established as 1-10 cells per reaction. The novel PCR system was used to examine H. pylori distribution in oral specimens (40 inflamed pulp tissues, 40 saliva samples) collected from Japanese children, adolescents, and young adults. PCR analysis revealed that the detection rate of H. pylori in inflamed pulp was 15%, whereas no positive reaction was found in any of the saliva specimens. Taken together, our novel PCR system was found to be reliable for detecting H. pylori. The results obtained showed that H. pylori was detected in inflamed pulp but not saliva specimens, indicating that an infected root canal may be a reservoir for H. pylori.
4. 经过“筛查和治疗”防治策略后玻利维亚儿童和成人幽门螺杆菌的复发情况
Helicobacter. 2014 Oct;19(5):343-8. doi: 10.1111/hel.12137. Epub 2014 May 16.
Recurrence of Helicobacter pylori infection in Bolivian children and adults after a population-based "screen and treat" strategy.
Sivapalasingam S1, Rajasingham A, Macy JT, Friedman CR, Hoekstra RM, Ayers T, Gold B, Quick RE.
背景：
基于人群的“筛查和治疗”根除项目是通过降低高感染率、低收益的地区幽门螺杆菌感染从而预防胃癌的战略之一。
方法：
使用尿素呼气试验对两个村庄的居民进行了HP感染的检测，并对感染者予以监测下的药物治疗，在治疗后及1年后复查呼气试验。
结果:
我们检测了玻利维亚农村两个村庄的1153人中的1,065人(92%) 。幽门螺杆菌感染基线是80% (95% 可信区间[CI]: 78-84)。监测下的药物治疗年龄特异的根除率是相似的(≥92%)。治愈的患者中12% (95% CI: 8-15)感染复发。两个村庄5岁以下、5-9岁、10-14岁、大于等于15岁患者幽门螺杆菌年感染率分别为20% (95% CI: 10-29)、20% (95% CI: 10-29), 8% (95% CI: 1-15)和8% (95% CI: 4-12)。小于五岁的患者(odds ratios [OR] 2.7, 95% CI: 1.2-5.8)及5-9岁的患者(OR 2.7, 95% CI: 1.4-5.1)与大于等于15岁的患者相比更易复发。
结论：
结果显示小于十岁的儿童感染复发率较高，提示这一幽门螺杆菌的根除策略并不适用于高感染率、低收益的地区。
译者点评：本文结果提示在高感染率、低收入地区的幽门螺杆菌再感染率较高。
Abstract
BACKGROUND:
Strategies to prevent gastric cancer by decreasing Helicobacter pylori infections in high-prevalence, low-income countries could include a population-based "screen and treat" eradication program.
METHODS:
We tested residents of two rural villages for H. pylori infection using urea breath test (UBT), treated infected persons using directly observed therapy (DOT), retested for cure, and retested after 1 year later for H. pylori infection.
FINDINGS:
We tested 1,065 (92%) of 1153 residents from two villages in rural Bolivia. Baseline H. pyloriprevalence was 80% (95% confidence interval [CI]: 78-84). Age-specific cure rates were similar (≥92%) after DOT. Among those cured, 12% (95% CI: 8-15) had recurrent infection. Age-specific annual H. pylorirecurrence rates for combined villages were 20% (95% CI: 10-29) in persons <5 years, 20% (95% CI: 10-29) in 5-9 years, 8% (95% CI: 1-15) in 10-14 years, and 8% (95% CI: 4-12) in persons ≥15 years. Compared with the referent population, those ≥15 years, recurrent infections were significantly more likely in children <5 years (odds ratios [OR] 2.7, 95% CI: 1.2-5.8) and 5-9 years (OR 2.7, 95% CI: 1.4-5.1).
INTERPRETATION:
Children <10 years had high H. pylori recurrence rates following a population-based screen and treat program; this H. pylori eradication strategy may not be feasible in high-prevalence, low-income settings.
5. 初诊为儿童炎症性肠病的患者的幽门螺杆菌相关性胃炎的发病情况
Helicobacter. 2014 Oct;19(5):400-5. doi: 10.1111/hel.12141. Epub 2014 May 14.
The prevalence of Helicobacter pylori gastritis in newly diagnosed children with inflammatory bowel disease.
Roka K1, Roubani A, Stefanaki K, Panayotou I, Roma E, Chouliaras G.
背景：
最近的研究显示，炎症性肠病（IBD）的患者幽门螺旋杆菌感染率较低。该研究旨在比较希腊初诊IBD的儿童与未患有IBD的儿童的幽门螺杆菌（+/-）胃炎的发病情况。
材料和方法：
该回顾性研究对象为2002-2011年间初次行消化内镜检查的儿童。研究对象分为四组：克罗恩病患者（CD），溃疡性结肠炎（UC），未分类炎症性肠病患儿（IBDU）及非炎症性肠病患儿（non-IBD）。通过培养阳性或组织学阳性及CLO试验明确幽门螺杆菌诊断。对于培养阴性或未能培养的及仅一个方法阳性（组织学或CLO）的患儿进一步行尿素呼气试验以评估，阳性者纳入感染组。
结果：
我们研究了159 名IBD患者(66 CD, 34 UC, and 59 IBDU) 及1209名非IBD患者。幽门螺杆菌相关胃炎在IBD组发病率较低(IBD组3.8% vs 对照组13.2% ，p < .001)， IBD患儿年纪显著大于非IBD儿童(p < .001)。幽门螺杆菌阴性胃炎患儿属于IBD组的可能性是幽门螺杆菌阳性胃炎患儿的3.3倍(p = .006)。
结论：
IBD患儿组幽门螺杆菌胃炎的发生低于对照组。我们的研究证实幽门螺杆菌感染和IBD的负相关性。我们需要进一步辨别到底幽门螺杆菌的保护作用还是IBD患童既往抗生素的使用产生的效果。
译者小结：与大部分研究结果类似，儿童幽门螺杆菌感染与IBD呈负相关。
Abstract
BACKGROUND:
Recent studies have shown that patients with inflammatory bowel disease (IBD) are less likely to be infected with Helicobacter pylori compared with non-IBD patients. We aimed to study the prevalence of H. pylori-positive and H. pylori-negative gastritis in newly diagnosed children with IBD in comparison to those with non-IBD in Greece.
MATERIALS AND METHODS:
All children who underwent first esophagogastroduodenal endoscopy between 2002 and 2011 were retrospectively included. Four groups were studied: patients with Crohn's disease (CD), ulcerative colitis (UC), IBD unclassified (IBDU), and non-IBD individuals (non-IBD). Helicobacter pylori infection was defined by positive culture or by positive histology and CLO test. Those children with negative or not available culture and only one positive test (histology or CLO) were further evaluated by urea breath test, and the positives were also included in the infected group.
RESULTS:
We studied 159 patients with IBD (66 CD, 34 UC, and 59 IBDU) and 1209 patients in non-IBD individuals. Helicobacter pylori gastritis was less frequent in the IBD group (3.8% vs 13.2% in the control group, p < .001), whereas IBD patients were significantly older than non-IBD children (p < .001). Children with H. pylori-negative gastritis were 3.3 times more likely to belong in the IBD group compared with H. pylori-positive patients (p = .006).
CONCLUSIONS:
Occurrence of H. pylori gastritis is less frequent in children with IBD compared with controls. Our study confirms an inverse association between H. pylori and IBD. Future studies are needed to distinguish between a true protective role of H. pylori and a confounding effect due to previous antibiotic use in children with IBD.
6. 综述：益生菌在幽门螺旋杆菌感染治疗的临床应用
J Microbiol Immunol Infect. 2014 Oct;47(5):429-37. doi: 10.1016/j.jmii.2013.03.010. Epub 2013 Jun 10.
Clinical application of probiotics in the treatment of Helicobacter pylori infection--a brief review.
Patel A1, Shah N2, Prajapati JB2.
越来越多文献报道益生菌在幽门螺旋杆菌感染治疗中的作用，可作为抗生素的替代或补充，可能可以减少抗生素的用量从而减轻其副作用。尽管抗生素为基础的根除幽门螺杆菌治疗方案90%是有效的，但十分昂贵并且会产生耐药性，可能伴随很多副作用。体外实验中益生菌对幽门螺杆菌有抑制作用。动物实验表明益生菌能有效治疗幽门螺杆菌相关的胃内炎症。近十二个人类研究支持益生菌联合抗生素治疗的疗效，十六个研究单独使用益生菌用于幽门螺杆菌感染作为抗生素的替代治疗。大多数研究表明使用益生菌后幽门螺杆菌相关胃炎好转且胃内幽门螺杆菌负荷量减少。然而，尚未有研究表明仅靠益生菌可以根除幽门螺杆菌。联合益生菌可以减少幽门螺杆菌根除治疗过程中的副作用，对患者有益。长期服用含益生菌株制品可对人的幽门螺杆菌感染有益，尤其可以减少由严重胃内炎症导致症状的风险。
译者点评：益生菌对幽门螺杆菌相关胃炎的益处体现在两方面：一是可以减轻炎症程度缓解症状，二是可提高根除治疗的成功率并降低不良反应发生率。
Abstract
The role of probiotics in the treatment of gastrointestinal infections is increasingly being documented as an alternative or complement to antibiotics, with the potential to decrease the use of antibiotics or reduce their side effects. Although antibiotics-based Helicobacter pylori eradication treatment is 90% effective, it is expensive and causes antibiotic resistance associated with other adverse effects. Probiotics have an in vitro inhibitory effect on H. pylori. Animal studies demonstrated that probiotic treatment is effective in reducing H.pylori-associated gastric inflammation. About 12 human studies investigated the efficacy of combinations of antibiotics and probiotics, whereas 16 studies used probiotic alone as an alternative to antibiotics for the treatment of H. pylori infection. Most of the studies showed an improvement of H. pylori gastritis and decrease in H. pylori colonization after administration of probiotics. However, no study could demonstrate complete eradication of H. pylori infection by probiotic treatment. Probiotic combinations can reduce adverse effects induced by H. pylori eradication treatment and, thus, have beneficial effects in H. pylori-infected individuals. Long-term intakes of products containing probiotic strains may have a favorable effect on H. pylori infection in humans, particularly by reducing the risk of developing disorders associated with high degrees of gastric inflammation.