含米诺环素和奥硝唑的四联疗法联合双歧杆菌乳杆菌三联活菌片根除幽门螺杆菌的效果

目的 研究含米诺环素及奥硝唑的四联疗法的有效性和安全性,并分析双歧杆菌乳杆菌三联活菌片(金双歧)在幽门螺杆菌根除治疗中的效果,指导临床实践。 方法 回顾性分析2018年5月至2019年5月福建省立医院收治的101例幽门螺杆菌阳性患者,所有患者均采用艾司奥美拉唑+米诺环素+奥硝唑+铋剂四联方案,其中51例患者联合金双歧治疗,比较各类患者治疗效果及不良反应。通过13C尿素呼气试验评估幽门螺杆菌根除情况。不良反应及临床症状缓解情况通过访谈进行评估。 结果 101例患者幽门螺杆菌总根除率为94.06%(95% CI:87.01%~97.56%),共出现不良反应19例,不良反应率为18.81%(95% CI:11.98%~28.07%)。90.10%的患者依从性良好。联合和不联合金双歧的患者其幽门螺杆菌根除率差异无统计学意义(92.2% vs 96.0%,P=0.678 0),临床症状缓解情况差异也无统计学意义(P=0.444 0),但联合金双歧可减少治疗不良反应发生率(P=0.005 0)。 结论 含米诺环素和奥硝唑的四联疗法是根除幽门螺杆菌有效且耐受性良好的方案。补充金双歧不能提高患者根除率,但可以减少治疗时的不良反应。     

Inhibition of Helicobacter pylori Infection in Humans by Lactobacillus reuteri ATCC 55730 and Effect on Eradication Therapy: A Pilot Study

Background:  Several studies report an inhibitory effect of probiotics on Helicobacter pylori .
Aim:  To test whether Lactobacillus reuteri ATCC 55730 reduces H. pylori intragastric load in vivo, decreases dyspeptic symptoms, and affects eradication rates after conventional treatment.
Materials and Methods:  In a double-blind placebo-controlled study, 40 H. pylori -positive subjects were given L. reuteri once a day for 4 weeks or placebo. All underwent upper endoscopy, ¹³C-urea breath test, and H. pylori stool antigen determination at entry and ¹³C-urea breath test and H. pylori stool antigen (used as both qualitative and semiquantitative markers) after 4 weeks of treatment. Sequential treatment was administered subsequently to all.
Results:  In vivo, L. reuteri reduces H. pylori load as semiquantitatively assessed by both ¹³C-urea breath test δ -value and H. pylori stool antigen quantification after 4 weeks of treatment ( p <  .05). No change was shown in patients receiving placebo. L. reuteri administration was followed by a significant decrease in the Gastrointestinal Symptom Rating Scale as compared to pretreatment value ( p <  .05) that was not present in those receiving placebo ( p =  not significant). No difference in eradication rates was observed.
Conclusions:  L. reuteri effectively suppresses H. pylori infection in humans and decreases the occurrence of dyspeptic symptoms. Nevertheless, it does not seem to affect antibiotic therapy outcome.     

The effects of probiotics on PPI-triple therapy for Helicobacter pylori eradication

Background: This study was performed to evaluate whether the addition of probiotics to proton pump inhibitor (PPI)‐based triple therapy increases the likelihood of successful Helicobacter pylori eradication. Materials and Methods: Three hundred and forty‐seven H. pylori‐infected patients were randomized into a triple‐plus‐yogurt group (yogurt group, n = 168) or a triple‐only group (control group, n = 179). Triple therapy consisted of PPI b.i.d., clarithromycin 500 mg b.i.d., and amoxicillin 1 g b.i.d. for 7 days. Yogurt group received triple therapy for 1 week and one bottle of Will yogurt per day for at 3 weeks, starting on the first day of triple therapy. Will yogurt (a Korean brand) contains Lactobacillus acidophilus HY2177, Lactobacillus casei HY2743, Bifidobacterium longum HY8001, and Streptococcus thermophilus B‐1. ¹³C‐urea breath test was performed at least 4 weeks after completion of triple therapy. Eradication rates, compliances, and adverse events were compared. Results: By intention‐to treat analysis the H. pylori eradication rates in the yogurt group 79.2% (133 of 168) was similar to that in the control group 72.1% (129 of 179) (p = .124). However, by per‐protocol (PP) analysis, the eradication rate in the yogurt group, 87.5% (133 of 152) was higher than that in the control group, 78.7% (129 of 164) (p = .037). Common adverse events were metallic taste (11.8%) and diarrhea (8.6%). The frequency of adverse effects in the yogurt group 41.1% (69/168) were higher than in the control group, 26.3% (47 of 179) (p = .003). However, most adverse events were mild to moderate in intensity, and the severities of adverse effects were similar in both groups (p = .401). Conclusions: The addition of Will yogurt to triple therapy did not reduce the side‐effects of triple therapy. But it increased the H. pylori eradication rate by PP analysis, encouraging more research in this field.     

Probiotic containing Lactobacillus reuteri DSM 17648 as an adjunct treatment for Helicobacter pylori infection: A randomized,double-blind,placebo-controlled trial

Background

Despite multiple therapy regimens, the decline in the Helicobacter pylori eradication rate poses a significant challenge to the medical community. Adding Lactobacillus reuteri probiotic as an adjunct treatment has shown some promising results. This study aims to investigate the efficacy of Lactobacillus reuteri DSM 17648 in H. pylori eradication and its effect in ameliorating gastrointestinal symptoms and adverse treatment effects.

Materials and Methods

This randomized, double-blinded, placebo-controlled trial involved treatment-naïve H. pylori-positive patients. Ninety patients received standard triple therapy for 2 weeks before receiving either a probiotic or placebo for 4 weeks. The posttreatment eradication rate was assessed via a ¹⁴C urea breath test in Week 8. The Gastrointestinal Symptom Rating Scale (GSRS) questionnaire and an interview on treatment adverse effects were conducted during this study.

Results

The eradication rate was higher in the probiotic group than in the placebo group, with a 22.2% difference in the intention-to-treat analysis (91.1% vs. 68.9%; p = 0.007) and 24.3% difference in the per-protocol analysis (93.2% vs. 68.9%; p = 0.007). The probiotic group showed significant pre- to post-treatment reductions in indigestion, constipation, abdominal pain, and total GSRS scores. The probiotic group showed significantly greater reductions in GSRS scores than the placebo group: indigestion (4.34 ± 5.00 vs. 1.78 ± 5.64; p = 0.026), abdominal pain (2.64 ± 2.88 vs. 0.89 ± 3.11; p = 0.007), constipation (2.34 ± 3.91 vs. 0.64 ± 2.92; p = 0.023), and total score (12.41 ± 12.19 vs. 4.24 ± 13.72; p = 0.004). The probiotic group reported significantly fewer adverse headache (0% vs. 15.6%; p = 0.012) and abdominal pain (0% vs. 13.3%; p = 0.026) effects.

Conclusions

There was a significant increase in H. pylori eradication rate and attenuation of symptoms and adverse treatment effects when L. reuteri was given as an adjunct treatment.     

含益生菌四联疗法根治顽固性幽门螺杆菌感染的疗效观察

目的 探讨含益生菌四联疗法根治顽固性幽门螺杆菌感染(H.pylori)的疗效.方法 经标准三联疗法根治失败的顽固性幽门螺杆菌感染患者180例,随机分为6组:A组(含双歧杆菌乳杆菌三联活菌片四联疗法):雷贝拉唑+阿莫西林+克拉霉素+双歧杆菌乳杆菌三联活菌片;B组(伴同疗法):雷贝拉唑+阿莫西林+克拉霉素+呋喃唑酮;C组(标准四联疗法):雷贝拉唑+阿莫西林+克拉霉素+胶体果胶铋.疗程均为7d.同样分组方案A1组、B1组、C1组,疗程14d.治疗前后查肝肾功及三大常规,观察药物不良反应.1个月后复查胃镜并作快速尿素酶实验及14C呼吸实验(14C-UBT),观察H.pylori根除情况.结果 含双歧杆菌乳杆菌三联活菌片四联疗法根除率7d为76.7％,与其他两组比较差异无统计学意义(P＞0.05),无任何不良反应发生;14 d为90.0％,与其他两组比较差异也无统计学意义(P＞0.05),各组均优于7天组(P ＜0.05);14天组不良反应发生率为6.67％,7天及14天组不良反应均低于其他相应各组.结论 含双歧杆菌乳杆菌三联活菌片四联疗法根治顽固性幽门螺杆菌感染的疗效与标准四联及伴同疗法相当,但不良反应较少,可以值得推广.     

益生菌与幽门螺杆菌对黏膜屏障的影响及其机制的研究进展

消化系黏膜屏障对致病菌有防御功能,但是在根除幽门螺杆菌(H. pylori)过程中会导致黏膜屏障的破坏。大量研究表明,益生菌通过修复上皮细胞以及细胞间连接、减少黏液分泌和炎症反应以及缓解消化道菌群紊乱等方式修复黏膜屏障。本文主要综述幽门螺杆菌对消化系黏膜屏障的损害及其机制,以及益生菌对黏膜屏障损伤的保护及修复机制研究的进展。     

H.pylori抗体鸡蛋制品对H.pylori感染BALB/c小鼠的实验研究

目的通过幽门螺杆菌(Helicobacter pylori,H.pylori)标准株的接种,建立BALB/c小鼠感染H.pylori胃炎动物模型,评价H.pylori抗体鸡蛋制品对小鼠感染性胃炎的预防效果。方法将灭活的H.pylori国际标准菌株(NCTC 11637)作为抗原,对产蛋鸡进行免疫。免疫后收集鸡蛋,对达到效价的鸡蛋,无菌采集卵黄。BALB/c小鼠60只,适应性喂养1周后,随机分为5组,Ⅰ组为胃炎模型组,Ⅱ组为生理盐水组,Ⅲ、IV、V组分别为低剂量、中剂量和高剂量卵黄抗体组,每组12只。Ⅰ组予H.pylori菌液灌胃造模,Ⅱ组先予生理盐水灌胃后再予H.pylori菌液灌胃对照,Ⅲ、IV、V组分别用不同剂量抗H.pylori卵黄抗体灌胃后再予H.pylori菌液灌胃造模。小鼠均于距最后一次灌胃后8周全部处死,用微需氧细菌培养检测H.pylori定植;HE染色观察小鼠胃黏膜病理组织学改变。结果在接种H.pylori后第8周,Ⅰ组和Ⅱ组小鼠胃内均有大量H.pylori定植,感染率为91.7%,Ⅲ组的感染率是58.3%,IV和V组的感染率均小于30%。结论 H.pylori抗体鸡蛋制品可以抑制BALB/c小鼠感染H.pylori,抗体的保护作用与抗体的剂量呈正相关。     

Inhibition of binding of Helicobacter pylori to the glycolipid receptors by probiotic Lactobacillus reuteri

We examined the competition of binding of Lactobacillus reuteri and Helicobacter pylori to gangliotetraosylceramide (asialo-GM1) and sulfatide which are putative glycolipid receptor molecules of H. pylori, and identified a possible sulfatide-binding protein of the L. reuteri strain. Among nine L. reuteri strains, two (JCM1081 and TM105) were shown to bind to asialo-GM1 and sulfatide, and to inhibit binding of H. pylori to both glycolipids by a thin layer chromatogram-overlay assay using biotin-labeled bacterial cells. The extract from the bacterial cells of strain TM105 with several detergents, including octyl beta-D-glucopyranoside, retained binding to both glycolipids and also inhibited H. pylori binding, suggesting that a binding inhibitor(s) is associated with the bacterial cell surface. When the cell extract was applied to the agarose gel immobilized galactose 3-sulfate corresponding to the structure of sugar moieties of sulfatide, an approximately 47-kDa protein was found to bind to the gel. This observation strongly suggested that inhibition by selected L. reuteri strains help to prevent infection in an early stage of colonization in H. pylori and proposed that L. reuteri strains sharing glycolipid specificity with H. pylori have a potential as probiotics.     

Pediatric Helicobacter pylori infection and circulating T-lymphocyte activation and differentiation

Background: In this study, H. pylori‐infected and noninfected children with gastritis were compared to a control group with respect to circulating CD4⁺ and CD8⁺ T lymphocytes expressing activation and differentiation markers. Additionally, the lymphocyte phenotypes of children with gastritis were correlated with the gastric inflammation scores. Materials and Methods: H. pylori infection status was assessed based on [¹³C]urea breath test, rapid urease test, and histology. Analysis of the lymphocyte surface molecule expression was carried out by triple‐color flow cytometry. Results: The group of H. pylori‐infected children showed an elevated proportion of peripheral B cells with CD19^low, along with a twofold increase in the percentage of memory (CD45RO⁺) CD4⁺ and CD8⁺ T‐cell subsets (p < .05). Moreover, a positive correlation between the age and the percentage of these subsets was seen (r = .38, p = .04 and r = .56, p < .01, respectively). Children with gastritis but without infection had a slightly increased percentage of CD8⁺ T cells and CD56⁺ NK cells, CD3^high T cells and CD45RO^high CD4⁺ T‐cell subsets (p < .05). Both H. pylori‐infected and noninfected children with gastritis were characterized by an increased percentage of memory/effector CD4⁺ T cells, the presence of NK cells with CD56^high, memory T‐cell subset with CD4^high, and naive, memory, memory/effector, and effector T‐cell subsets with CD8^high (p < .05). Gastric inflammation scores correlated positively with the percentage of CD4⁺ T lymphocytes in H. pylori‐infected children (r = .42, p = .03). In noninfected children, gastric inflammation scores correlated positively with the percentage of B cells (r = .45, p = .04). Conclusion: In H. pylori‐negative children, gastritis was associated with an increased percentage of activated NK and T cells, and intermediate‐differentiated peripheral blood CD4⁺ T cells, which was more pronounced in H. pylori‐positive children who also showed an increased B‐cell response. However, increased inflammation was only associated with the elevation of CD4⁺ T‐cell percentage in H. pylori‐positive children as well as B‐cell percentage in H. pylori‐negative children with gastritis.     

数学模型法研究L．casei LC2W对H.pylori SS1黏附MKN-45细胞的抑制作用

目的研究干酪乳杆菌LC2W对幽门螺杆菌（H.pylori）SS1黏附MKN-45的抑制作用,探讨益生菌对致病菌拈抗的机制。方法体外培养人胃癌细胞MKN-45,采用平板计数的方法研究2株细菌的黏附性质;引入数学模型,比较LC2W与H.pylori SS1的竞争、排除和替代作用。结果运用模型可以估算出LC2W和H.pylori SS1对MKN-45最大黏附数和亲和力的大小,并可以预测在混合体系中2种菌黏附的比例;实验发现LC2W对H.pylori SS1的黏附具有很强的竞争作用和排除作用,且这2种作用存在明显的量效关系。LC2W对H.pylori SS1的黏附的替代作用不明显或过程非常缓慢。结论所采用的数学模型能较好的模拟LC2W和H.pylori SS1黏附及LC2W对H.pylori SS1黏附抑制作用,这种抑制作用主要是通过竞争性占位形成的。     

Gastric and duodenum microflora analysis after long-term Helicobacter pylori infection in Mongolian Gerbils

Background: Long‐term Helicobacter pylori infection leads to chronic gastritis, peptic ulcer, and gastric malignancies. Indigenous microflora in alimentary tract maintains a colonization barrier against pathogenic microorganisms. This study is aimed to observe the gastric and duodenum microflora alteration after H. pylori infection in Mongolian Gerbils model. Materials and Methods: A total of 18 Mongolian gerbils were randomly divided into two groups: control group and H. pylori group that were given H. pylori NCTC J99 strain intragastrically. After 12 weeks, H. pylori colonization was identified by rapid urease tests and bacterial culture. Indigenous microorganisms in stomach and duodenum were analyzed by culture method. Histopathologic examination of gastric and duodenum mucosa was also performed. Results: Three of eight gerbils had positive H. pylori colonization. After H. pylori infection, Enterococcus spp. and Staphylococcus aureus showed occurrences in stomach and duodenum. Lactobacillus spp. showed a down trend in stomach. The levels and localizations of Bifidobacterium spp., Bacteroides spp., and total aerobes were also modified. Bacteroides spp. significantly increased in H. pylori positive gerbils. No Enterobacteriaceae were detected. Positive colonization gerbils showed a higher histopathologic score of gastritis and a similar score of duodenitis. Conclusions: Long‐term H. pylori colonization affected the distribution and numbers of indigenous microflora in stomach and duodenum. Successful colonization caused a more severe gastritis. Gastric microenvironment may be unfit for lactobacilli fertility after long‐term H. pylori infection, while enterococci, S. aureus, bifidobacteria, and bacteroides showed their adaptations.     

Probiotic Lactobacillus fermentum UCO-979C biofilm formation on AGS and Caco-2 cells and Helicobacter pylori inhibition

The ability of the human isolate Lactobacillus fermentum UCO-979C to form biofilm and synthesize exopolysaccharide on abiotic and biotic models is described. These properties were compared with the well-known Lactobacillus casei Shirota to better understand their anti-Helicobacter pylori probiotic activities. The two strains of lactobacilli synthesized exopolysaccharide as detected by the Dubois method and formed biofilm on abiotic and biotic surfaces visualized by crystal violet staining and scanning electron microscopy. Concomitantly, these strains inhibited H. pylori urease activity by up to 80.4% (strain UCO-979C) and 66.8% (strain Shirota) in gastric adenocarcinoma (AGS) cells, but the two species showed equal levels of inhibition (~84%) in colorectal adenocarcinoma (Caco-2) cells. The results suggest that L. fermentum UCO-979C has probiotic potential against H. pylori infections. However, further analyses are needed to explain the increased activity observed against the pathogen in AGS cells as compared to L. casei Shirota.     

The influence of Lactobacillus brevis on ornithine decarboxylase activity and polyamine profiles in Helicobacter pylori-infected gastric mucosa

Background. Functional probiotics may prevent Helicobacter pylori infection, and some evidence suggests that they also possess antitumor properties. Lactobacillus brevis (CD2) is a functional Lactobacillus strain with peculiar biochemical features, essentially related to the activity of arginine deiminase. This enzyme catalyzes the catabolism of arginine and affects the biosynthesis of polyamines (putrescine, spermidine, and spermine). Polyamines are polycations found in high concentrations in both normal and neoplastic cells. Our aims were: 1, to assess whether oral administration of L. brevis (CD2) affects H. pylori survival in the human gastric mucosa; 2, to evaluate the effects of L. brevis (CD2) on polyamine biosynthesis in gastric biopsies from H. pylori‐positive patients. Materials and Methods. For 3 weeks before endoscopy, 22 H. pylori‐positive dyspeptic patients randomly received (ratio 1 : 1) high oral doses of L. brevis (CD2) or placebo. Before and after treatment, H. pylori infection was determined by urea breath test (UBT). In gastric biopsies, ornithine decarboxylase activity and polyamine levels were, respectively, evaluated by a radiometric technique and high‐pressure liquid chromatography (HPLC). Results. L. brevis (CD2) treatment did not eradicate H. pylori. However, a reduction in the UBT delta values occurred, suggesting a decrease in intragastric bacterial load. Significantly, L. brevis (CD2) induced a decrease in gastric ornithine decarboxylase activity and polyamine levels. Conclusions. Our data support the hypothesis that L. brevis (CD2) treatment decreases H. pylori colonization, thus reducing polyamine biosynthesis. Alternatively, the arginine deiminase activity following L. brevis (CD2) administration might cause arginine deficiency, preventing polyamine generation from gastric cells.     

幽门螺杆菌感染诊断方法的比较

目的:考核各种H.pylori感染诊断方法,试图证明分离培养仍是细菌性感染诊断的最可靠方法.方法:315例胃十二指肠疾病患者同时进行胃活检组织分离培养,病理切片找菌,快速脲酶试验,14CO2呼气试验检查,比较它们之间的检出率差异.结果:四种方法各自的总检出率差异无显著性.以分离培养为金标准,其他方法的误诊误治率可达12.06%～22.22%.各种诊断方法对H.pylori感染的实际检出率差异存在着显著性.结论:本研究提示,分离培养应为H.pylori感染临床诊断的金标准.     

CagA and VacA are immunoblot markers of past Helicobacter pylori infection in atrophic body gastritis

BACKGROUND AND AIM: Atrophic body gastritis (ABG) may be induced by H. pylori infection. It is difficult to diagnose H. pylori infection in this condition, since during progression of body atrophy the bacterium disappears. In 30% of patients with ABG no sign of H. pylori infection is detectable. We aimed to investigate whether patients with ABG, classified as H. pylori-negative by conventional methods (ELISA serology and Giemsa stain histology), have been previously exposed to the infection. METHODS: Case series consisted of 138 outpatients with ABG, of whom 31 are H. pylori negative (histology and ELISA serology), and 107 are H. pylori related (histology and ELISA serology positive: active infection, n = 29; only serology positive: past infection, n = 78). Thirty control subjects who were H. pylori negative at histology and ELISA serology were investigated. Immunoblotting of sera against H. pylori whole-cell protein lysate was performed. RESULTS: None of the control sera recognized CagA, VacA, heat-shock protein B, and urease B, yielding a specificity of 100%. All H. pylori-negative patients with ABG showed immunoblotting seroreactivity, including in each case either CagA or VacA. The concomitant seroreactivity against CagA and VacA was highly prevalent in the H. pylori-negative patients with ABG, comparable to those with active infection (77.4% vs. 86.2%) and with past infection (vs. 61.5%). CONCLUSIONS: Immunoblotting against CagA and VacA is able to prove past exposure to H. pylori infection in all patients with ABG defined as H. pylori-negative by conventional methods, suggesting a hidden role of H. pylori infection in gastric atrophy also in these patients.     

乳杆菌治疗幽门螺杆菌感染疗效的Meta分析

目的 系统评价乳杆菌治疗幽门螺杆菌（H. pylori）感染的有效性。方法 计算机检索PubMed、Cochrane Central Register of Controlled Trials、Clinicatrials.gov、中国临床试验注册中心（http://www.chictr.org.cn/）、中国知网（CNKI）、万方数据库。检索时间从建库至2016年6月30日。此外追索已纳入文献和综述的参考文献。经两位研究者独立筛选文献、提取资料和评价质量,交叉核对后,采用Stata 12.0进行Meta分析。结果 最终纳入17个RCT,共1 758例患者。Meta分析结果：乳杆菌联合常规三联疗法能提高H. pylori根除率[OR=2.762,95%CI(2.163,3.526),P<0.001],降低不良反应发生率[OR=0.334,95%CI(0.242,0.461),P<0.001],但乳杆菌单独应用对H. pylori根除率结果与对照组比较差异无统计学意义。根据乳杆菌给药疗程的亚组分析结果,0~14（含14）d乳杆菌联合给药方案显著提高了H. pylori根除率[OR=2.893,95%CI(2.187,3.827),P<0.05],14~28（含28）d给药疗程也显著提高了H. pylori根除率[OR=2.619,95%CI(1.652,4.153),P<0.05]。乳杆菌联合三联疗法在欧洲人群及亚洲人群的亚组分析中,均提高了H. pylori根除率。结论 乳杆菌联合三联疗法有利于提高H. pylori根除率,并能降低总不良反应的发生,在H. pylori感染相关疾病的治疗中具有一定意义。