Probiotics as a Novel Treatment for Non-Alcoholic Fatty Liver Disease; A Systematic Review on the Current Evidences

Context

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, with 5-10% of liver having extra fat. Increase in its prevalence in all age groups is linked with obesity and Type II diabetes. The treatment of NAFLD remains controversial. A growing body of evidence suggests a relation between overgrowth of gut microbiota with NAFLD and non-alcoholic steatohepatitis (NASH). The objective of this review is to provide an overview on experimental and clinical studies assessing all positive and negative effects of probiotics.

Evidence Acquisition

We made a critical appraisal on various types of documents published from 1999 to March 2012 in journals, electronic books, seminars, and symposium contexts including Medline, PubMed, and Cochrane Central Register of Controlled Trials databases. We used the key words: “non-alcoholic fatty liver disease, probiotics, non-alcoholic steatohepatitis, liver disease, and fatty liver”.

Results

Probiotics, as biological factors, control the gut microbiota and result in its progression. It is in this sense that they are suggestive of a new and a natural way of promoting liver function. Correspondingly, limited evidence suggests that probiotics could be considered as a new way of treatment for NAFLD.

Conclusions

Various experimental studies and clinical trials revealed promising effects of probiotics in improving NAFLD; however given the limited experience in this field, generalization of probiotics as treatment of NAFLD needs substantiation through more trials with a larger sample sizes and with longer-term follow up.     

复合益生菌制剂对急性坏死性胰腺炎大鼠的保护作用

背景:肠道细菌易位是重症急性胰腺炎(SAP)时胰腺坏死感染的主要来源,因此保护肠黏膜屏障对SAP的治疗具有重要意义。目的:探讨复合益生菌制剂对急性坏死性胰腺炎(ANP)大鼠肠黏膜屏障和胰腺损伤的保护作用。方法:50只SPF级大鼠随机分为假手术组(n=10)、ANP模型组(n=20)和益生菌干预组(n=20)。采用胰腺被膜下均匀注射牛磺胆酸钠制备ANP模型,干预组术前30 min以双歧杆菌四联活菌片溶液灌胃。术后6 h采集标本,检测血淀粉酶、二胺氧化酶(DAO)、TNF-α水平,观察胰腺组织病理学表现和末端回肠组织超微结构。结果:ANP模型组血淀粉酶、DAO、TNF-α水平和胰腺组织学评分均显著高于假手术组(P<0.05),益生菌干预组各项指标均较ANP模型组有所改善(P<0.05)。假手术组末端回肠黏膜结构完整;ANP模型组回肠黏膜上皮细胞微绒毛萎缩、排列稀疏,细胞间连接松弛;益生菌干预组微绒毛稍稀疏,细胞间连接紧密度较ANP模型组增高。结论:复合益生菌制剂对ANP大鼠具有保护作用,不仅能减轻肠黏膜损伤,保护肠黏膜屏障功能,还能减轻胰腺局部损伤和全身性炎症反应。     

序贯疗法和三联疗法联合益生茵根除幽门螺杆菌感染的临床对照研究

背景：近年来,幽门螺杆菌（Hp）对抗菌药物耐药的问题日益突出,研究者正不断尝试调整根除治疗方案以提高根除率。目的：评估序贯疗法和三联疗法联合益生菌根除Hp感染的疗效和安全性。方法：纳入有消化不良症状、RUT和“C-UBT均阳性且既往未接受过Hp根除治疗的患者,进入不同组别。序贯疗法组（A组,n=127）：前5d雷贝拉唑10mgbid＋阿莫西林1．0gbid,后5d雷贝拉唑10mgbid＋克拉霉素500mgbid＋替硝唑400mgbid;三联疗法＋益生菌组（B组,n=117）：（雷贝拉唑10mgbid＋阿莫西林1．0gbid＋克拉霉素500mgbid）×7d,三联活菌胶囊3粒tid×14d;标准三联疗法组（C组,n=106）：PPI和抗菌药物的剂量、用法、疗程同B组,但不加用益生菌。疗程结束后4周复查“C-UBT,同时评估症状改善和溃疡愈合情况。治疗期间观察不良反应发生情况。结果：A、B两组Hp根除率（ITT分析：82．7％、78．6％对63．2％;PP分析：83．3％、79．3％对65．0％）和症状缓解率（82．7％、84．6％对65．1％）均显著高于C组（P〈0．05）,A、B组问差异无统计学意义。三种方案的消化性溃疡痊愈率无明显差异（72．7％、67．6％和45．5％,P〉0．05）。B组不良反应发生率显著低于A、C两组（4．3％对15．0％和20．8％,P〈0．05）。结论：与标准三联疗法相比,序贯疗法和三联疗法联合益生菌能明显提高Hp根除率,其中三联疗法联合益生菌安全性更高,可能更适用于临床。     

Anti-inflammatory potential of the probiotic dietary supplement Lactibiane Tolérance: in vitro and in vivo considerations

BACKGROUND & AIMS: Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. In inflammatory bowel disease (IBD), where major modifications of the intestinal microflora have been reported, there is an increasing interest in modulating the flora with probiotic products. This work addresses the anti-inflammatory potential of Lactibiane Tolérance, a probiotic dietary supplement (mixture of four strains) using in vitro and in vivo approaches. METHODS: Comparison of the four individual strains and the commercial product reconstituted from them was conducted by in vitro tests (cytokine release after 24h stimulation of human peripheral blood mononuclear cells (PBMC)). The potential immunomodulatory characteristics of Lactibiane Tolérance were determined in vivo in an acute mice model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Assessment of colitis included blinded histological and macroscopic scores. RESULTS: We showed that Lactibiane Tolérance has anti-inflammatory properties in vitro by stimulating IL-10 production and in vivo by conferring a significant protective effect in the TNBS-induced colitis model (more than 50% decrease of colitis symptoms, P<0.01). CONCLUSIONS: These results demonstrate that a probiotic dietary supplement, Lactibiane Tolérance, can significantly prevent the initial injury of TNBS and could stimulate the initiation of clinical trials in IBD.     

益生菌在过敏性疾病中的应用及作用机制

益生菌通过促进树突状细胞释放细胞因子,改变Th1/Th2平衡,使免疫反应向Th1细胞方向进行,抑制Th2细胞反应,从而增强宿主的免疫功能.研究表明益生菌在特异性皮炎、哮喘及过敏性鼻炎等IgE相关过敏性疾病的预防和治疗中发挥一定的作用,但由于过敏性疾病的病因复杂、诱因众多,目前益生菌对其作用尚无一致的结论,需进一步进行循证医学研究.     

益生菌预防新生儿呼吸机相关性肺炎的临床疗效研究

目的 探讨阻断新生儿呼吸机相关性肺炎(ventilator associated pneumonia,VAP)胃-肺感染途径的方法,降低VAP发生率.方法 将机械通气的80例新生儿分为2组,治疗组(40例)鼻饲益生菌(双歧杆菌),对照组(40例)不干预.观察2组患儿VAP发生率、胃液pH值、胃细菌定植及其与VAP病原学的同源性.结果 治疗组和对照组患儿VAP发生率分别为12.5％ (5/40)和47.5％( 19/40),两组比较差异有统计学意义(x2=10.21,P＜0.01);治疗组患儿VAP发生时间[(5.4±2.1)d]明显晚于对照组[(4.3±1.0)d](t=3.2,P＜0.01).治疗组患儿予机械通气第7天胃液pH值≤3的比率(80.0％,32/40)明显高于对照组(47.5％,19/40)(x2=11.5,P＜0.01);而胃细菌定植率(30.0％,12/40)明显低于对照组(80.0％,32/40)(x2=16.9,P＜0.01);治疗组VAP病原菌与胃定植菌同源率(40.0％,2/5)明显低于对照组(78.9％,15/19)(x2=8.7,P＜0.01).结论 肠道益生菌能降低新生儿胃液pH值,抑制胃内细菌定植,延迟VAP发生时间,降低VAP发生率.     

微生态制剂(金双歧)联合乳果糖治疗儿童功能性便秘78例疗效分析

目的:探讨微生态制剂(金双歧)联合乳果糖治疗小儿功能性便秘的疗效。方法:78例患儿随机分为两组,治疗组40例,对照组38例。对照组给予一般治疗,治疗组在其基础上加服金双歧和乳果糖口服液。结果:治疗组总有效率为92.50%,对照组总有效率为60.53%,治疗组疗效优于对照组(P<0.01)。结论:微生态制剂联合乳果糖治疗小儿功能性便秘短期疗效显著,值得推荐,且应注重个体化、综合性治疗,关注远期疗效。     

肠道微生态和老龄化

肠道微生态在保持宿主健康、提供能量和营养素,抵抗生物体侵袭方面具有重要作用。研究表明,老年人肠道菌群中兼性厌氧菌数量增加,厌氧乳酸杆菌等厌氧菌和双歧杆菌等有益菌数量减少,菌群物种多样性降低。这些变化均会导致结肠内腐败代谢活动增多,使老年人对疾病的易患性增加。现对近年来老年人肠道微生态的研究以及益生菌在老年人口中的应用情况进行总结,以提高对老年人肠道微生态相关研究的重视。     

双歧三联活菌对体外循环心脏直视手术患者肠黏膜屏障功能的影响

目的 探讨双歧三联活菌对体外循环心脏直视手术患者肠黏膜屏障功能的影响.方法 择期拟行体外循环下瓣膜置换术患者40例,年龄30～64岁,体重40～80 Kg,ASA分级Ⅱ或Ⅲ级,采用随机数字表法,将患者随机分为对照组(C组)和双歧三联活菌组(Y组),每组20例.Y组于术前7d开始,每日口服双歧三联活菌制剂(每片含活菌数0.5×107 CFU)4片,每日3次,连服7 d.分别于体外循环前(T1)、主动脉开放10 min(T2)、停体外循环即刻(T3)、术后2、6和18 h(T4～6)时采集中心静脉血样5 ml,采用紫外分光光度法测定血浆二胺氧化酶(DAO)活性和D-乳酸浓度,酶联免疫吸附法测定血浆IL-6和IL-10的浓度.结果 与T1时比较,两组其余时点血浆DAO活性和D-乳酸IL-6和IL-10浓度均升高(P＜0.05);与C组比较,Y组T2～5时血浆DAO活性和D-乳酸浓度降低,T4,5时血浆IL-6和IL-10浓度降低(P＜0.05).结论 双歧三联活菌可在一定程度上抑制炎性反应,改善体外循环心脏直视手术患者的肠黏膜屏障功能.

Abstract：

Objective To investigate the effects of probiotics on the plasma diamine oxidase (DAO) activity and D-lactate, IL-6 and IL-10 levels in patients undergoing open heart surgery under cardiopulmonary bypass (CPB) , trying to elucidate the mechanism of protective effect of probiotics against CPB- induced injury to intestinal mucosal barrier. Methods Forty ASA Ⅱ - Ⅲ patients of both sexes aged 30-64 yr weighing 40-80 kg undergoing open heart operation under CPB were randomized into 2 groups ( n = 20 each) : control group (group C) and probiotics group (group Y) . Group Y received Jinshuangqi (Bifid Triple Viable containing bifido-bacterium, lacto-bacillus, streptococcus thermophiles) 4 pills 3 times a day for 7 days before operation. Venous blood samples were taken from CVP line before operation (T1 ), at 10 min after aortic unclamping (T2 ) and at the end of CPB (T3 ) and at 2, 6, 18 h (T4,5,6) after operation for determination of plasma DAO activity and D-lactate, IL-6 and IL-10 levels.Results Plasma DAO activity, D-lactate, IL-6 and IL-10 levels were significantly increased after CPB was started at T2-6 as compared with the baseline values at T1 in both groups. Plasma DAO activity and D-lactate level were significantly lower at T2-5 , the plasma IL-6 level was significantly lower and plasma IL-10 level higher at T4,5 in group Y than in group C. Conclusion Probiotics can protect intestinal mucosal barrier in patients undergoing open heart surgery under CPB and attenuate inflammatory response.     

Gut microbiota,dysbiosis and colon lavage

Gut microbial dysbiosis is considered an alteration of diversity and abundance of intestinal microbes, which contributes to the onset of many disorders. Several factors cause dysbiosis, depending on life-style (nutrition, stress, environment, smoking, physical activity) or particular diseases (inflammatory, autoimmune, chronic diseases). Drugs (i.e. antibiotics, anticancer drugs), as well as medical and surgical procedures, can often cause dysbiosis. Mechanical bowel preparations (MBP) and the so called "bowel cleansing" have an immediate impact on intestinal microbial composition. Whether these "acute" changes may lead to any clinical consequences is still unknown. It is tempting to speculate that such dysbiosis fostering events, at least in patients already presenting abdominal complaints, such as irritable bowel syndrome (IBS), or inflammatory bowel disease (IBD) patients, may drive additional or more severe symptoms. Recently, the possibility of using probiotic supplementation has been addressed in the literature, with the purpose to counteract intestinal dysfunctional changes observed in relation to a dysbiotic state. Whereas probiotics are recognized to be effective and safe in restoring gut microbiota dysbiosis, preliminary evidence suggest that this approach may prove helpful even in case of transient dysbiotic states related to colonoscopy bowel preparation.