基于VOSviewer的肝硬化肠道微生态研究的可视化分析——

分析肝硬化肠道微生态的研究现状、热点及前沿趋势。

检索Web of Science（WOS）核心数据库建库至2020年12月31日的肝硬化肠道微生态研究的英文文章。通过文献计量分析软件VOSviewer分析发文国家、机构、作者和本研究领域的热点和前沿方向。

共检索到848篇文章。美国的Virginia Commonwealth University是肝硬化肠道微生态相关文章发表最多的机构。国外学者Bajaj JS在该领域发文量最高。肝硬化肠道微生态相关研究在《Hepatology》上的发表数量最多,为48篇。研究热点可概括为肝性脑病、代谢性肝病、菌群失衡与炎症感染等。

通过对肝硬化肠道微生态研究热点和新兴趋势进行可视化分析,为肝硬化肠道微生态的研究人员及研究单位提供了研究方向及潜在合作可能。

     

益生菌补充剂治疗绝经后骨质疏松症或骨量减少的系统评价

系统评价益生菌补充剂对绝经后骨质疏松症（PMOP）或骨量减少的有效性及安全性。

选取8个公共数据库,检索自建库至2022年9月,无语言限制,使用随机对照方法,评估补充益生菌补充剂对腰椎、股骨颈、总髋关节骨密度（BMD)、T值（T-value）、胶原降解产物（CTX）、I型前胶原氨基端前肽（PINP）、骨碱性磷酸酶（BALP）、骨钙素（BGP）水平和不良反应率的影响。

纳入了8篇RCT文献,647名参与者,治疗组有325名,对照组322名。结果显示益生菌组在提高PMOP和绝经后骨量减少患者的腰椎BMD、股骨颈BMD、T值、BGP和降低绝经后妇女CTX、BALP等方面显著优于对照组（P＜0.05）。亚组分析结果显示益生菌治疗PMOP患者后显著提高腰椎BMD、股骨颈BMD、全髋关节BMD、T值和降低CTX、BALP优于对照组（P＜0.05）。

益生菌干预PMOP和骨量减少患者后显著提高骨密度及降低骨代谢,对PMOP患者的作用更显著。

     

益生菌治疗类风湿关节炎的meta分析和试验序贯分析

系统评价益生菌治疗类风湿关节炎的临床疗效。

检索中国生物医学数据库、中国知网、万方、维普、Embase、PubMed、the Cochrane Library、Web of Science数据库,时间均从建库至2021年7月,对公开发表的益生菌治疗类风湿关节炎的随机对照试验进行meta分析和试验序贯分析。

共纳入6项研究,总样本量242例。Meta分析显示,益生菌治疗类风湿关节炎能显著降低CRP[MD = ‒2.26,95% CI = （‒4.30,‒0.23）,P = 0.03]和TNF-α[MD = ‒1.78,95% CI = （‒2.73,0.83）,P＜0.01]水平,提高IL-10[MD = 3.80,95% CI = （0.40,7.19）,P = 0.03]水平,而ESR、IL-1β、IL-6、MDA、TAC、DAS28、TJC、SJC、HAQ和ACR20等水平均与安慰剂相当。敏感性分析显示结果较为稳健,试验序贯分析显示CRP的获益具有结论性,Egger检验显示不存在发表偏倚（P = 0.17）。

益生菌能够有效降低CRP和TNF-α水平,提高IL-10水平,具有治疗类风湿关节炎的潜力。

     

口服微生态制剂对早产低体重新生儿坏死性小肠结肠炎的预防效果

分析口服微生态制剂预防早产低体重新生儿坏死性小肠结肠炎（NEC）的效果。

采用随机数字表法将我院2021年2月至2022年3月收治入院的82例早产低体重新生儿分为观察组和对照组,各41例。对照组患儿予以常规对症治疗,观察组在此基础上予以口服微生态制剂预防治疗。对比两组早产儿NEC发生率和手术率,干预前后免疫球蛋白（IgG、IgM、IgA）水平变化情况,肠道菌群变化情况。

观察组患儿NEC发生率为7.32%,显著低于对照组的24.39%（P＜0.05）。干预后观察组患儿IgG、IgM、IgA水平高于对照组,组间差异均有统计学意义（均P＜0.05）。干预后观察组患儿肠道细菌总数、球菌总数、杆菌总数高于对照组（均P＜0.05）。干预7 d、14 d后,两组患儿体质量均有所增加,且观察组患儿体质量高于对照组（均P＜0.05）。观察组患儿达到完全肠内营养时间短于对照组（P＜0.05）。

口服微生态制剂可有效降低早产低体重新生儿NEC的发生率,促进早产儿肠道菌群稳定,增强患儿免疫能力,对改善早产低体重新生儿预后具有重要的意义。

     

益生菌治疗口腔假丝酵母菌感染效果的meta分析

通过循证医学的方法评价益生菌治疗口腔假丝酵母菌感染的效果。

计算机检索PubMed、EMbase、Web of Science、The Cochrane Library、中国知网、维普数据库、万方数据库和中国生物医学文献数据库中关于益生菌治疗口腔假丝酵母菌感染效果的随机对照试验,检索时限为建库至2021年8月18日,由2名研究者独立对文献进行资料提取和质量评价,采用RevMan 5.4统计软件对提取完成后的资料进行meta分析。

共纳入12篇研究,其中英文研究4篇,中文研究8篇,纳入研究对象1 029人,其中试验组537人,对照组492人。研究结果显示,益生菌能有效治疗口腔假丝酵母菌感染[OR=7.80,95% CI（4.78,12.75）,P＜0.000 1],降低口腔假丝酵母菌检出率[OR=0.06,95% CI（0.01,0.57）,P=0.010 0],降低治愈后复发率[OR=0.21,95% CI（0.12,0.35）,P＜0.000 1]。

益生菌对治疗口腔假丝酵母菌感染具有一定效果,能降低口腔中假丝酵母菌的定植,减低治愈后的复发率。

     

双歧杆菌三联活菌散/胶囊治疗儿童抗生素相关性腹泻临床疗效的meta分析

采用meta分析评价双歧杆菌三联活菌散/胶囊治疗儿童抗生素相关性腹泻的临床疗效。

系统性地检索中国知网、维普、万方、PubMed、Embase及Web of Science数据库,纳入国内外使用双歧杆菌三联活菌散/胶囊治疗儿童抗生素相关性腹泻的随机对照研究和前瞻性非随机对照临床试验,文献检索时间至2022年6月,筛选所检索文献,提取符合纳入标准的文献数据进行质量评价,采用Cochrane协作网提供的RevMan 5.3软件进行meta分析。

经系统地检索文献,本研究共纳入16项前瞻性非随机对照研究进行meta分析,共计1 415例儿童,meta分析结果显示使用双歧杆菌三联活菌散/胶囊治疗儿童抗生素相关性腹泻的显效率显著高于对照组[OR＝2.58,95% CI（2.03,3.28）,I² = 10%,P＜0.000 1];治疗组的总体有效率也显著高于对照组[OR = 5.80,95% CI（3.80,8.85）,I² = 0%,P＜0.000 1]。

Meta分析评价现有文献结果表明双歧杆菌三联活菌散/胶囊与常规治疗措施相比,能够显著提高儿童抗生素相关性腹泻的显效率和总体有效率,有助于改善患儿临床预后和加速康复。

     

益生菌联用泻药对中国成人功能性便秘的疗效——基于随机对照试验的Meta分析

探讨国内益生菌联合泻药对于成人功能性便秘的疗效。

以“益生菌”和“功能性便秘”为关键词, 分别在中国知网、维普、万方数据库、中国生物医学文献数据系统、PubMed、Embase和Cochrane Library检索益生菌联合泻药对功能性便秘的疗效, 检索时限从建库至2020年12月6日。采用Stata 13.1和RevMan 5.4软件进行Meta分析。

共检索出16 929篇文献, 最终纳入23篇文献。联合组在有效率[OR=4.39, 95%CI=(3.25, 5.92), P < 0.000 01]、排便频率改善[WMD=0.77, 95%CI=(0.16, 1.38), P < 0.000 01]、粪便性状改善[WMD=1.12, 95%CI=(0.87, 1.37), P < 0.000 01]等方面均优于对照组。

益生菌联合泻药比单用泻药更能有效缓解便秘。

     

益生菌联合药食同源材料改善常用抗结核药所致小鼠肝损伤和肠道菌群紊乱的作用

探讨益生菌与药食同源材料补充对异烟肼、利福平、乙胺丁醇和吡嗪酰胺4种抗结核药联用所致小鼠肝损伤及肠道菌群紊乱的影响。

将30只SPF级雄性ICR小鼠随机分为对照组、模型组和治疗组, 每组10只, 其中模型组和治疗组小鼠给予4种抗结核药建立肝损伤模型, 治疗组在此基础上给予益生菌联合药食同源材料组方。持续灌胃2周后每组随机抽取5只小鼠处死取材。剩余小鼠停止抗结核药灌胃, 仅继续给予组方灌胃1周。检测血清中生化指标丙氨酸氨基转氨酶(ALT)、天冬氨酸氨基转移酶(AST)、三酰甘油(TG)、总胆固醇(TC)、总胆红素(TBiL)、尿酸(UA)及白蛋白(Alb)水平。采用流式细胞术分析各组5只小鼠脾脏免疫细胞亚群比例。提取结肠内容物DNA, 采用16S rDNA测序分析各组肠道菌群构成。

益生菌联合药食同源材料可显著减轻抗结核药联用导致的小鼠ALT、AST、TC及TBiL水平的增加, 同时缓解抗结核药联用导致的小鼠脾脏CD3⁺ T、CD4⁺ T细胞的减少。与模型组相比, 治疗组小鼠肠道乳杆菌属和拟杆菌属相对丰度略有增加, 葡萄球菌属相对丰度显著降低。第21天治疗组小鼠肠道菌群Alpha多样性与模型组相比显著增加。

益生菌联合药食同源材料对抗结核药联用所致的肝损伤及肠道菌群紊乱具有一定改善作用, 且随干预时间的延长效果更明显。

     

益生菌粉（副干酪乳酪杆菌207-27）的毒理学安全性评价

评估益生菌粉（副干酪乳酪杆菌207-27）的毒理学安全性,为其应用提供依据。

通过大鼠急性经口毒性试验、细菌回复突变试验、小鼠红细胞微核试验、小鼠精母细胞染色体畸变试验及大鼠28 d经口毒性试验研究益生菌粉（副干酪乳酪杆菌207-27）的安全性。

大鼠急性经口毒性试验结果显示,益生菌粉（副干酪乳酪杆菌 207-27）对大鼠的经口急性毒性LD₅₀均大于15.00 g/（kg•BW）,根据急性毒性分级标准属实际无毒。细菌回复突变试验、小鼠红细胞微核试验及小鼠精母细胞染色体畸变试验结果均显示阴性。大鼠28 d经口毒性试验结果表明,实验组大鼠体质量、摄食量、食物利用率、眼部状况、血液学指标、血液生化指标、脏器指数、大体及病理学检查结果与对照组相比差异均无统计学意义。

益生菌粉（副干酪乳酪杆菌207-27）具有良好的毒理学安全性。

     

益生菌联合铋剂四联法根除幽门螺杆菌的Meta分析和试验序贯分析

采用Meta分析和试验序贯分析的方法评估益生菌辅助铋剂四联法根除幽门螺杆菌的有效性和安全性。

检索PubMed、the Cochrane Library、Embase、Web of Science、中国知网、维普数据库、万方、中国生物医学数据库, 检索时限均从数据库建立至2021年3月, 对公开发表的关于益生菌联合铋剂四联法根除幽门螺杆菌的随机对照双盲试验进行Meta分析和试验序贯分析。

共纳入6项研究, 总样本量1 462例。与铋剂四联法相比, 益生菌联合铋剂四联法能有效提高幽门螺杆菌根除率[RR=1.15, 95%CI=(1.03, 1.29), P=0.02], 并显著降低不良反应率[RR=0.45, 95%CI=(0.25, 0.82), P=0.01], TSA显示其结果均具有确切的结论性。Harbord回归显示不存在显著发表偏倚。GRADE证据质量评价显示, 幽门螺杆菌根除率、恶心、腹泻、味觉异常的证据质量均为中, 不良反应率、呕吐、腹痛、便秘、腹胀、厌食、疲劳、头晕的证据质量为低。

益生菌联合铋剂四联法是根除幽门螺杆菌更为安全有效的治疗方案, 具有进一步研究探索的价值。

     

Gut Microbiota,Prebiotics, Probiotics,and Synbiotics in Management of Obesity and Prediabetes: Review of Randomized Controlled Trials

Objective: To review the data from randomized controlled trials (RCTs) for the roles of microbiota, pre-, pro- and synbiotics in metabolic conditions (obesity, prediabetes, and diabetes mellitus type 2 [DM2]).Methods: Primary literature was reviewed on the topics including RCTs of pre-, pro- and synbiotics use for metabolic disease.Results: Gut bacteria (microbiota) benefit digestion and have multiple other functions. Microbiota could increase harvesting of energy from the food and cause subclinical inflammation seen in metabolic disorders. Diet-related interventions including prebiotics, probiotics, and synbiotics (combining pre-and probiotics) may benefit metabolic conditions. Prebiotics are complex carbohydrates (i.e., dietary fiber). Results of RCTs of prebiotics suggested a neutral effect on body weight, decreased fasting and postprandial glucose, and improved insulin sensitivity and lipid profile. Some inflammation markers were reduced, sometimes substantially (20–30%). RCTs for probiotics demonstrated significant but small effects on body weight (<3%) and metabolic parameters. The effect was seen mostly with fermented milk or yogurt compared to capsule form, consumption for at least 8 weeks, and use of multiple rather than a single bacterial strain. Changes in microbiota were seen at times with both pre- and probiotics. Pickled and fermented foods, particularly vegetables and beans, could serve as a dietary source of pre-, pro-, and synbiotics. These foods showed possible benefits for morbidity and mortality in prospective cohort studies.Conclusion: Pre-, pro-, and synbiotics could prove useful, but further research is needed to clarify their clinical relevance for the prevention and management of metabolic disease.Abbreviations:A1c = glycohemoglobin A1cCI = confidence intervalCVD = cardiovascular diseaseGMB = gut (large bowel) microbiotaDM2 = diabetes mellitus type 2HOMA-IR = homeostatic model assessment of insulin resistanceLDL = low-density lipoproteinLPS = lipopolysaccharideNAFLD = nonalcoholic fatty liver diseaseRCT = randomized controlled trialSMD = standardized mean differenceTG = triglycerides     

Modulation of gut microbiome in nonalcoholic fatty liver disease: pro-, pre-, syn-, and antibiotics

Nonalcoholic fatty liver disease (NAFLD) is one of the most common types of liver diseases worldwide and its incidence continues to increase. NAFLD occurs when the body can no longer effectively store excess energy in the adipose tissue. Despite the increasing prevalence of NAFLD, making lifestyle changes, including increased exercise, is often an elusive goal for patients with NAFLD. The liver directly connects to the gut-gastrointestinal milieu via the portal vein, which are all part of the gut-liver axis. Therefore, the gut-microbiome and microbial products have been actively studied as likely key factors in NAFLD pathophysiology. Hence, dysbiosis of the gut microbiome and therapeutic manipulation of the gut-liver axis are being investigated. Novel therapeutic approaches for modulating gut microbiota through the administration of probiotics, prebiotics, synbiotics, and antibiotics have been proposed with numerous promising initial reports on the effectiveness and clinical applications of these approaches. This review delves into the current evidence on novel therapies that modulate gut microbiota and discusses ongoing clinical trials targeting the gut-liver axis for the management and prevention of NAFLD.     

In vitro effects of selected synbiotics on the human faecal microbiota composition

Synbiotics are recognized means of modulating gut microbiota composition and activities. However, whether synbiotics are superior to prebiotics and probiotics alone in moderating the gut microbiota towards a purportedly healthy composition has not been determined. Eight selected synbiotics (short-chain fructooligosaccharides or fructooligosaccharides, each combined with one of four probiotics, Lactobacillus fermentum ME-3, Lactobacillus plantarum WCFS1, Lactobacillus paracasei 8700:2 or Bifidobacterium longum 46) were added to 24-h pH-controlled anaerobic faecal batch cultures. The prebiotic and probiotic components were also tested alone to determine their respective role within the synbiotic for modulation of the faecal microbiota. Effects upon major groups of the microbiota were evaluated using FISH. Rifampicin variant probiotic strains were used to assess probiotic levels. Synbiotic and prebiotics increased bifidobacteria and the Eubacterium rectale-Clostridium coccoides group. Lower levels of Escherichia coli were retrieved with these combinations after 5 and 10 h of fermentation. Probiotics alone had little effect upon the groups, however. Multivariate analysis revealed that the effect of synbiotics differed from the prebiotics as higher levels of Lactobacillus-Enterococcus were observed when the probiotic was stimulated by the prebiotic component. Here, the synbiotic approach was more effective than prebiotic or probiotic alone to modulate the gut microbiota.     

Dysbacteriosis and preparations with probiotic function

Information on intestinal microecological disturbances (dysbacteriosis) and the preparations of probiotics, prebiotics and synbiotics used for the correction of resident normal colon microflora is presented. Probiotics are preparations containing live microbes or substances of microbial origin that, when introduced by natural methods are expected to confer beneficial physiologic, biochemical and immune effects to the host through the stabilization and the optimization of functions of normal microflora. Prebiotics are preparations containing a non-digestible food ingredient that beneficially affect the host by selectively stimulating the growth and the activity of a limited number of resident bacteria of normal microflora in the colon. Synbiotics are preparations obtained as the result of the rational combination of probiotics and prebiotics.     

Prebiotics,Prosynbiotics and Synbiotics: Can They Reduce Plasma Oxidative Stress Parameters? A Systematic Review

This study assessed the effectiveness of presybiotics, prosybiotics and synbiotics on reducing serum oxidative stress parameters. PubMed/Medline, Ovid, Google Scholar, ISI Web of Science and SCOPUS were searched up to September 2016. English language randomized clinical trials reporting the effect of presybiotics, prosybiotics or synbiotic interventions on serum oxidative stress parameters in human adults were included. Twenty-one randomized clinical trials met the inclusion criteria for systematic review. Two studies investigated prebiotics, four studies synbiotics and fifteen studies probiotics. According to our systematic review, prebiotic could decrease malondialdehyde and increase superoxidative dismutase, but evidence is not enough. In comparison with fructo-oligosaccharide, inulin is much more useful for oxidative stress reduction. Using probiotics with dairy products could reduce oxidative stress significantly, but probiotic in form of supplementation did not have any effect on oxidative stress. There is limited but supportive evidence that presybiotics, prosybiotics and synbiotics are effective for reducing oxidative stress parameters. Further randomized clinical trials with longer duration of intervention especially on population with increased oxidative stress are needed to provide more definitive results before any recommendation for clinical use of these interventions.     

益生菌的治疗现状与前景以及 对呼吸道有益菌探索的研究进展

益生菌是调节机体微生态失衡的有效途径。肝功能异常影响肠道微生物,慢性肝衰竭、2型糖尿病、动脉粥样硬化相关心血管疾病等与肠道微生态失衡密切相关。同时肠道菌群亦受环境、遗传等复合条件影响,改变菌群组成可能导致疾病的发生发展。提倡益生菌对疾病的预防、治疗、预后,改善机体微环境,提高生命质量。近年来,益生菌、益生元、合生元三方面的研究飞速发展,对肠道益生菌研发已经取得一定成果。呼吸道作为与外界相通的腔道其优势菌群已经有相关报道,但对呼吸道益生菌的探索尚不明确,呼吸道内的优势菌是否可以制成益生菌制剂尚有待研究。     

益生菌、益生元对慢性肾脏疾病治疗的研究进展

益生菌是近些年来的研究热点,其对人体的有益作用越来越被关注,其在治疗众多疾病上有显著效果,本文将分析和总结益生菌对慢性肾脏疾病（chronic kidney disease,CKD）方面的重要影响。益生菌通过黏液层、上皮层、肠相关淋巴组织这三个层次对肠道进行作用,并且增加黏液和上皮细胞紧密连接以及上皮细胞的存活力来增强肠道屏障,而且又可以发挥营养作用。在其对CKD的影响中,益生菌、益生元和合生元可以降低尿毒症毒素,也可以减少免疫炎症的反应,提高肾功能和生活质量。益生菌组合剂量、益生菌与益生元组合方式都会影响益生菌制剂的效果,并且个体肠道的差异以及抗生素的使用等也都对实验有影响。本综述包括了益生菌对CKD的潜在作用机制和研究方法的进展,对以后精准医疗模式下防治CKD提供新的思路和靶点。     

Prebiotics and synbiotics: towards the next generation

Recent research in the area of prebiotic oligosaccharides and synbiotic combinations with probiotics is leading towards a more targeted development of functional food ingredients. Improved molecular techniques for analysis of the gut microflora, new manufacturing biotechnologies, and increased understanding of the metabolism of oligosaccharides by probiotics are facilitating development. Such developments are leading us to the time when we will be able to rationally develop prebiotics and synbiotics for specific functional properties and health outcomes.     

纳米枸杞多糖合生元靶向微生态调节剂的制备及质量研究

目的制备合生元结肠靶向微生态调节剂,并建立其质量标准。方法球磨法制备枸杞多糖纳米粒,并将其与双歧杆菌、结肠粘附材料按一定比例装填入结肠靶向胶囊中,制备成合生元结肠靶向微生态调节剂;苯酚-硫酸法测定制剂中多糖含量,平板活菌计数法检测制剂中活菌数量。结果球磨法制备的枸杞多糖纳米粒成类球形,表面圆整,无粘连,80％粒径集中在464nm;合生元结肠靶向微生态调节剂符合2010版药典对胶囊剂的质量要求。结论按本法制备的合生元结肠靶向微生态调节剂安全可靠,其质量符合2010版药典对胶囊剂的质量要求。     

微生态制剂对化疗不良反应的影响

化疗是恶性肿瘤治疗的重要组成部分,是提高患者的生活质量和生存率的一种治疗手段。目前化疗的不良反应并不局限于恶心呕吐、腹痛、腹泻、乏力和贫血等常见的反应,更主要的是化疗药物会对胃肠道、肠黏膜以及肠道菌群等产生影响。微生态制剂包括益生菌、益生元和合生元等。微生态制剂作为一种能够促进机体正常生长的微生态调节剂,可以通过维持肠道微生态平衡来保持机体健康,微生态制剂还具有调节免疫和消除炎症等功能,从而减少宿主因化疗而产生的不良反应。