幽门螺杆菌根除疗法对肠道微生态的影响

幽门螺杆菌(Helicobacter pylori)感染是世界范围关注的焦点,进行幽门螺杆菌根除治疗是世界各国针对感染所采取的一项重要举措。但随着幽门螺杆菌耐药率,尤其是对大环内酯类药物耐药率的增加,标准三联疗法根除效果逐渐不能满足需求,更多的疗法得以推出。但是新推出的诸多疗法都应用了比以前更大剂量、更多种类甚至更长疗程的抗生素,这对于肠道微生物的微生态结构和数量都可能造成严重影响,甚至可能产生严重的副作用,同时也可能会对其耐药性产生影响。本文回顾了近20年来幽门螺杆菌根除治疗对肠道微生态的影响和一些新型实验疗法的研究结果,以对上述问题进行探讨。     

幽门螺杆菌感染对胃肠道菌群影响及其与胃部疾病相关性的研究进展

幽门螺杆菌(H.pylori)是一种定植在胃黏膜上皮的革兰阴性螺旋杆菌,可以诱发多种消化系统疾病,全球有一半以上的人感染H.pylori。在人体复杂而庞大的胃肠道微生态系统中,H.pylori可通过影响胃内环境来降低胃肠道菌群丰富度及多样性。胃肠道菌群与H.pylori共同作用,影响消化性溃疡、胃癌及缺铁性贫血等一系列消化系统疾病的发生发展,但其具体致病机制尚不明确。根除H.pylori可以提高胃肠道菌群的多样性,有助于预防H.pylori相关疾病的代际传播和进一步发展。H.pylori治疗期间补充益生菌可提高根除率,减少抗生素相关不良反应的发生。本文就H.pylori与胃肠道菌群关系的研究进展作一综述,以期探讨H.pylori的致病机制。     

慢性胃炎患者肠道菌群分析

探索慢性胃炎（CG）患者肠道菌群变化特点。

采集我院青年CG患者（CG组）和健康人群（NC组）的粪便样品,对其细菌16S rDNA V3—V4区域进行扩增并进行高通量测序,然后运用多种生物信息学手段进行分析。

CG组与NC组对象肠道菌群在门和科水平上均有不同之处,其中CG组对象有较高丰度的Actinobacteriota和较低丰度的Ruminococcaceae。CG组对象肠道菌群多样性及均一度均显著低于NC组（均P＜0.05）,但两者具有相似的丰富度水平。多元方差分析和相似性百分比分析均发现CG组和NC组对象肠道菌群有较大差异。Bifidobacterium、Blautia、Collinsella、Ruminococcus_torques_group和Streptococcus与CG患者密切相关。

CG患者的肠道菌群存在较大变化,其中Bifidobacterium、Blautia等细菌与CG的发生相关。

     

胃黏膜菌群与幽门螺杆菌的相关性

除幽门螺杆菌之外,胃黏膜内还定居着大量细菌,占主导地位的是厚壁菌门、变形菌门、拟杆菌门、放线菌门和梭杆菌门。幽门螺杆菌和胃黏膜菌群之间可通过竞争营养和空间、扰乱抑菌肽的分泌以及改变宿主胃生理环境等直接或间接相互影响。本研究总结了胃内正常菌群的组成特征,分析了胃黏膜菌群与幽门螺杆菌之间的相互关系及其潜在机制,并进一步探讨了胃黏膜菌群对幽门螺杆菌相关胃部疾病的影响,有利于深入理解慢性胃病的发病机制,为疾病预防及治疗提供理论依据。     

慢性胃炎患者胃黏膜菌群定位及定量分析

目的对慢性胃炎患者胃黏膜菌群进行定位及定量分析,探究其与胃炎及幽门螺杆菌(Helicobacter pylori,H.pylori)感染的相关性。方法收集58例慢性胃炎患者胃黏膜标本,提取胃黏膜菌群DNA,行荧光定量PCR定量胃黏膜总细菌及H.pylori,并进行相关性分析;另收集12例慢性胃炎患者胃黏膜标本石蜡包埋切片行荧光原位杂交定位胃黏膜菌群;慢性胃炎、肠化生程度的分类依据新悉尼分类系统。结果慢性胃炎患者胃黏膜细菌主要分布于胃黏膜表面、胃小凹及腺体中,细菌单个散在分布或聚集成团。多元线性回归分析显示胃黏膜总细菌数与性别、年龄、肠化生程度无关,与H.pylori感染、慢性胃炎程度有关(P0.05)。H.pylori阳性组胃黏膜总细菌数与H.pylori细菌数目呈明显正相关(r=0.536,P0.01)。不同胃炎程度之间胃黏膜总细菌数差异有统计学意义(P0.05),其中重度胃炎组胃黏膜总细菌数明显高于轻、中度胃炎组(P0.05、0.01)。不同肠化生程度之间胃黏膜总细菌数差异无统计学意义(P0.05)。H.pylori阳性组胃黏膜总细菌数明显高于阴性组(P0.01)。结论慢性胃炎患者胃黏膜菌群主要分布于胃黏膜表面、胃小凹及腺体中,细菌单个散在分布或聚集成团。胃黏膜菌群与慢性胃炎程度、H.pylori感染有关,与性别、年龄、肠化生程度无关,提示胃黏膜菌群的改变参与慢性胃炎的发展,H.pylori感染可改变胃黏膜菌群。     

幽门螺杆菌感染与脑梗死复发的关系及其机制研究

目的探讨幽门螺杆菌(HP)感染与脑梗死复发的相关性及其作用机制,为抗HP治疗降低脑梗死复发率提供依据。方法对我院神经内科收治的600例初发脑梗死患者,采用碳14呼气试验来定性HP感染患者,其中HP阴性患者197例为对照组(A组),HP阳性患者403例中,203例行标准三联疗法的患者为HP阳性治疗组(B组),200例未行抗HP治疗的患者为HP阳性观察组(C组)。所有患者均采用免疫投射比浊法定量血清超敏C反应蛋白(CRP),采用荧光偏振免疫测定法定量同型半胱氨酸(HCY),并进行为期3年的随访,比较3组患者的脑梗死复发率和CRP、HCY水平。结果 3组患者中,在随访期间复发率为HP阳性观察组为38.77%,HP阳性治疗组为25.37%,HP阴性对照组为20.51%。结论 HP感染与脑梗死有相关性,可通过作用于CRP和HCY加重动脉硬化,而增加脑梗死复发率。     

高脂血症患者肠道优势菌群与血清脂质水平相关性研究

目的探讨高脂血症患者肠道优势菌群变化及其与血清脂质水平的相关性。方法高脂血症患者及健康受试者各50例,采集其空腹血清样本和粪便样本,血清样本用于检测血清中总胆固醇（TC）、甘油-二酯（TG）和低密度脂蛋白胆固醇（LDL—C）的含量。应用实时定量PCR技术检测肠道内优势菌群的含量,并将其与血清脂质水平进行相关性分析。结果高脂血症患者肠道内总细菌量及拟杆菌属细菌较健康受试者组差异无统计学意义（P〉0．05）,而双歧杆菌属细菌、乳杆菌属细菌及粪杆菌属细菌较健康受试者明显降低（P〈0．05）,肠杆菌科细菌和肠球菌属细菌较健康受试者明显升高（P〈0．05）。高脂血症患者血清Tc与双歧杆菌属细菌、乳杆菌属细菌和粪杆菌属细菌呈现显著负相关,而与肠杆菌科细菌和肠球菌属细菌呈现显著正相关;血清LDL—C与双歧杆菌属细菌和粪杆菌属细菌呈现显著负相关,而与肠球菌属细菌呈现显著正相关;血清TG与双歧杆菌属细菌和乳杆菌属细菌呈现显著负相关,而与肠杆菌科细菌和肠球菌属细菌呈现显著正相关。结论高脂血症患者肠道优势菌群发生了明显的变化,血清脂质水平与肠道优势菌群变化具有显著相关性,提示肠道优势菌群结构的调整可改善患者血清脂质水平。     

牙斑幽门螺杆菌与慢性胃炎之间的关系

目的研究牙斑幽门螺杆菌与慢性胃炎之间的关系。方法对胃炎组、胃炎治疗组分别进行牙斑和胃黏膜幽门螺杆菌培养和比较。结果牙斑细菌培养：胃炎组阳性14例,阳性率为12．8％;治疗组阳性11例,阳性率为10．1％。胃黏膜细菌培养：胃炎组阳性47例,阳性率为43．1％;治疗组阳性19例,阳性率为17．4％。治疗前后比较牙斑标本差异无显著性（P〉0．05）,胃黏膜标本差异有非常显著性（P〈0．001）。结论牙斑中确实存在着幽门螺杆菌,而且是胃内反复感染的源泉,以致慢性胃病反复发作,难以治愈。     

胃黏膜定植乳酸杆菌对幽门螺杆菌感染的影响

目的探讨胃黏膜定植乳酸杆菌对幽门螺杆菌感染及胃黏膜菌群数量的影响。方法收集130例慢性胃炎患者胃窦黏膜组织,病理学检测幽门螺杆菌,提取胃黏膜基因组DNA,采用荧光定量PCR法检测乳酸杆菌和总细菌数。结果幽门螺杆菌阳性组和阴性组的乳酸杆菌检出率和乳酸杆菌数(Log)差异均无统计学意义(P0.05);乳酸杆菌阳性者和阴性者之间胃黏膜总细菌数(Log)差异无统计学意义(P0.05);乳酸杆菌细菌数(Log)与胃黏膜总细菌数(Log)无显著相关性(P0.05);不同炎症程度胃炎患者乳酸杆菌检出率差异无统计学意义(P0.05);肠化组和未肠化组乳酸杆菌检出率差异无统计学意义(P0.05);但是重度胃炎组幽门螺杆菌感染率和总细菌数量均显著高于轻度(P0.05)和中度胃炎组(P0.05)。结论胃黏膜定植乳酸杆菌对幽门螺杆菌的感染无影响,其存在与否及细菌数量对胃黏膜总细菌数亦无明显影响,并与胃炎炎症程度及肠化无关。乳酸杆菌不能通过抑制幽门螺杆菌定植、调节胃黏膜菌群而减轻炎症反应。     

布拉酵母菌辅助治疗对老年CagA和VacA阳性幽门螺杆菌感染患者IL-6和IL-8及肠道菌群的影响

评价布拉酵母菌（S. boulardii）对老年细胞毒素相关蛋白A（cytotoxin-associated gene A protein, CagA）和空泡毒素（vacuolating cytotoxin A, VacA）阳性幽门螺杆菌（H. pylori）感染患者炎症因子及肠道菌群的影响,以探讨S. boulardii治疗H. pylori I型高毒力株感染的机制。

选择我院200例CagA和VacA阳性的老年H. pylori感染者,采用随机数字表分成四联组和S. boulardii组。四联组患者采用铋剂四联疗法,S. boulardii组在铋剂四联疗法基础上加用S. boulardii。比较两组患者H. pylori根除率、胃黏膜组织学评分、临床疗效评分、不良反应、血清白细胞介素（IL）-6及IL-8水平、肠道菌群分布。

（1）S. boulardii组H. pylori根除率按方案（PP）分析和按意向性（ITT）分析均高于四联组（85.1% vs 72.8%;80.0% vs 67.0%）,差异均有统计学意义（均P＜0.05）。（2）S. boulardii组患者不良反应发生率（7.0%）低于四联组（21.0%）,差异有统计学意义（χ² = 8.140,P = 0.004）。（3）治疗后,两组患者胃黏膜组织学评分、临床症状评分、血清IL-6及IL-8水平均较治疗前降低,且S. boulardii组低于四联组（均P＜0.05）。（4）治疗后,四联组患者肠道乳杆菌、双歧杆菌数量较治疗前减少,肠杆菌、肠球菌数量较治疗前增加（均P＜0.05）;而S. boulardii组患者肠道乳杆菌、双歧杆菌数量较治疗前增加（均P＜0.05）,肠杆菌、肠球菌数量较治疗前差异无统计学意义（均P＞0.05）。

S. boulardii辅助四联疗法可提高老年患者H. pylori I型高毒力株的根除效果,减轻患者胃黏膜组织炎症,降低不良反应,其机制可能与S. boulardii下调免疫炎症介质表达和改善肠道菌群分布有关。

     

Persisting chronic gastritis and elevated Helicobacter pylori antibodies after successful eradication therapy

AIM: The persistence of chronic inflammation in gastric mucosa and elevated Helicobacter pylori antibodies after successful eradication therapy are common findings in clinical practice. We studied their possible association with each other and disappearance in long-term follow up, as well as their possible connection with gastric atrophy. PATIENTS AND METHODS: The study population consisted of 108 dyspeptic patients with successful eradication therapy median 6.4 years earlier. The patients underwent gastroscopy, and biopsies from antrum and corpus were evaluated by an experienced pathologist. Serum samples collected from 77 patients were studied for H. pylori antibodies, parietal cell antibodies, as well as for pepsinogen I, pepsinogen II, and gastrin-17 levels. RESULTS: The prevalence of chronic gastric inflammation and elevated H. pylori antibodies after successful eradication therapy decreased by time, but still after 5 years, 17 of 51 (33%) subjects had elevated H. pylori antibodies and 14 of 68 (21%) had a mild inactive chronic inflammation in gastric mucosa. In patients with and without chronic inflammation in gastric mucosa, elevated H. pylori antibodies were detected in three of 10 (30%) and 14 of 41 (34%), elevated parietal cell antibodies in one of 10 (10%) and six of 41 (15%), low pepsinogen I in one of 10 (10%) and none of 41, and elevated gastrin-17 in three of 10 (30%) and six of 41 (15%), respectively. CONCLUSION: More than 5 years after successful H. pylori eradication therapy, mild persistent chronic inflammation may occur in gastric mucosa in up to one-fifth and elevated H. pylori antibodies even in one-third of patients, although these two are independent phenomena.     

229例慢性胃炎患者幽门螺杆菌培养及耐药情况

目的了解慢性胃炎患者H.pylori感染及其耐药情况,为临床治疗提供参考。方法慢性胃炎患者胃镜活检标本培养分离H.pylori,对分离的H.pylori采用纸片扩散法进行耐药性检测。结果229例患者分离出97株H.pylori;H.pylori分离阳性率为42．36％（97／229）,其中男性分离率为43．79％（67／153）,女性分离率为39．47（30／76）;92株H.pylori对抗生素的耐药性分别为：甲硝唑8．7％,克拉霉素7．6％,阿莫西林1．1％、呋喃唑酮1．1％,阿奇霉素4．4％,左氧氟沙星0％。结论慢性胃炎患者H.pylori感染率较高,但与性别、年龄无关;慢性胃炎H.pylori对常用抗生素敏感,建议采用左氧氟沙星、阿莫西林、呋喃唑酮进行治疗。     

越鞠方加减联合益生菌对幽门螺杆菌阳性慢性胃炎患者的疗效

目的 探讨越鞠方加减联合益生菌对幽门螺杆菌(H.pylori)阳性慢性胃炎患者胃肠功能及血清血管活性肠肽(VIP)、生长激素释放肽(Ghrelin)的影响.方法 选取2017年6月至2019年6月我院收治的128例H.pylori阳性慢性胃炎患者为研究对象,采用随机数字表法分为研究组和对照组,各64例.两组患者均给予标...     

Long-term statin therapy affects the severity of chronic gastritis

Background: Helicobacter pylori (H. pylori) is a major cause of chronic gastritis. Statins have several pleotropic effects and their mechanisms of action could be related to anti‐inflammatory, antioxidants, and immunomodulatory effects. Aim: To determine whether statin therapy affects the severity of chronic gastritis. Materials and Methods: In a retrospective study, we evaluated 516 patients who underwent upper endoscopy. One‐hundred and ninety‐eight patients had chronic gastritis, The 198 patients with chronic gastritis were divided into two groups: group 1 comprised patients with a history of statin therapy and group 2 comprised patients with no history of statin therapy. Both groups were compared for age, gender, body mass index (BMI), underlying diseases, drug therapy, alcohol consumption, smoking and the serum levels of C‐reactive protein (CRP). The presence of H. pylori was determined by gastric biopsy and rapid urease test. The grade and severity of gastritis were assessed using the updated Sydney classification system in two gastric biopsy specimens that were taken from each participant in each group. Results: Of the 198 patients with chronic gastritis, 49% of the patients had mild gastritis and 51% had moderate to severe gastritis. From the results of a multiple logistic regression analysis after adjusting for confounding variables that included age, gender, and BMI, we found that elevated serum CRP levels (odds ratio (OR) 2.33; 95% confidence interval (CI) = 0.8–2.6, p = .02), H. pylori (OR 1.99; CI 0.14–2.4, p = .04), and the use of statin (OR 1.64; CI = 0.71–1.77, p = .05) independently predict the severity of chronic gastritis. Conclusion: Long‐standing statin therapy may reduce the severity of chronic gastritis. Mild increased CRP levels in absence of obvious source can predict the severity of chronic gastritis. Further researches are needed to assess the effect of statin in chronic gastritis.     

益生菌辅助四联疗法对H. pylori感染患者根治效果及肠道菌群的影响

研究益生菌辅助四联疗法对H. pylori感染患者根治效果及肠道菌群的影响。

选择2019年1月至2020年6月在我院接受治疗的160例H. pylori感染患者为研究对象,用随机数字表法分为对照组（n = 80）和观察组（n = 80）。对照组患者给予标准铋剂四联药物治疗,观察组加用双歧杆菌四联活菌片治疗。比较两组患者的H. pylori根除率、复发率、不良反应发生率、临床症状（上腹痛、上腹胀、嗳气、纳差）、肠道菌群（双歧杆菌、乳杆菌）和炎性因子[白细胞介素-6（IL-6）、白细胞介素-8（IL-8）及肿瘤坏死因子-α（TNF-α）]水平。

观察组患者的H. pylori根除率（95.00%）高于对照组（82.5%）,复发率和不良反应发生率低于对照组（均P＜0.05）。治疗后两组患者的临床症状积分均显著下降,同时观察组患者上腹痛、上腹胀、嗳气、纳差等临床症状积分低于对照组（均P＜0.05）。治疗后观察组患者肠道双歧杆菌和乳杆菌数量升高,而对照组降低,同时观察组患者肠道双歧杆菌和乳杆菌数量高于对照组（均P＜0.05）。治疗后观察组患者IL-6、IL-8和TNF-α水平均低于对照组（均P＜0.05）。

双歧杆菌四联活菌片辅助标准铋剂四联疗法治疗可显著提高H. pylori感染患者H. pylori根除率,降低复发率和不良反应的发生率,改善肠道菌群分布,减轻患者的临床症状和炎症状态。

     

幽门螺杆菌根除治疗对消化性溃疡患者血清胃泌素水平的影响

目的 观察幽门螺杆菌(H.pylori)根除治疗对消化性溃疡患者血清胃泌素水平的影响,为该病治疗提供参考。 方法 选择我院2017年8月至2019年8月收治的120例H.pylori感染的消化性溃疡患者作为观察组,根据H.pylori分型结果进一步分为HPⅠ型组和HPⅡ型组,观察组患者接受根除幽门螺杆菌治疗。选择同期入院的40例非幽门螺杆菌感染消化性溃疡患者作为对照组,对照组患者接受常规治疗。比较两组患者治疗效果、胃镜检查结果、H.pylori清除情况及血清胃泌素、IL10、IL17水平。 结果 HPⅠ型组、HPⅡ型组和对照组患者临床总有效率差异无统计学意义(92.75%、96.08%、97.50%,χ2=1.384,P=0.051)。HPⅠ型组、HPⅡ型组、对照组患者胃镜检查总有效率差异无统计学意义(91.30%,96.08%,97.50%,χ2=1.384,P=0.051)。HPⅡ型组患者幽门螺杆菌根除率高于HPⅠ型组(98.04% vs 85.51%,χ2=4.129,P=0.042)。HPⅠ型组患者治疗后血清胃泌素、IL10、IL17水平均高于对照组(均P结论 不同类型H.pylori感染消化性溃疡患者行幽门螺杆菌根除治疗后临床效果无显著差异。幽门螺杆菌根除治疗可降低消化性溃疡患者血清胃泌素、IL10、IL17水平。     

Resolution of gastrointestinal protein loss after Helicobacter pylori eradication in a patient with hypertrophic lymphocytic gastritis

BACKGROUND: Lymphocytic gastritis is a rare condition found in approximately 1% of dyspeptic patients. An association with Helicobacter pylori infection has been described. Hypertrophic lymphocytic gastritis is a rare cause of gastrointestinal protein loss. Here, we describe a patient with hypertrophic lymphocytic gastritis, in whom gastrointestinal protein loss resolved completely following H. pylori eradication. CASE REPORT: A 38-year old obese man without gastrointestinal symptoms showed a markedly decreased serum protein (53 g/l, normal 66-85 g/l), a decreased serum albumin (33 g/l, normal 35-52 g/l) and decreased serum immunoglobulin G and immunoglobulin M levels. A renal cause for protein loss was excluded, liver function was normal. Endoscopy of the upper gastrointestinal tract revealed enlarged rigid gastric folds, and an H. pylori-associated lymphocytic gastritis. 99mTc-labelled albumin scintigraphy showed an increased activity in the upper left abdomen compatible with protein secretion in the stomach, and tracer pooling in the upper small bowel. Push enteroscopy with histology demonstrated a normal upper small bowel. Two months after eradication therapy, cure of H. pylori infection was documented and serum protein (71 g/l) and albumin (41 g/l) had returned to normal, while lymphocytic gastritis was still present. One year after eradication therapy endoscopy of the upper gastrointestinal tract and histology and laboratory values were normal. CONCLUSION: Protein-losing gastropathy caused by H. pylori-associated hypertrophic lymphocytic gastritis can be cured solely by H. pylori eradication therapy.