Akkermansia muciniphila与代谢相关脂肪性肝病的研究进展

近年来,代谢相关脂肪性肝病(MAFLD)的发病率逐年升高,严重威胁人们的身心健康。肠道微生物可影响MAFLD的发生与演进,其中Akkermansia muciniphila(A.muciniphila)的发现已成为疾病干预的一个潜在靶点。肠道细菌A.muciniphila属于疣微菌门,是肠道中最丰富的细菌之一,丰度适宜的A.muciniphila定植可调节肠道屏障功能,发挥免疫应答,从而维持体内代谢平衡,然而该菌与MAFLD的关系及相关机制尚不明确。本文对Akkermansia muciniphila与代谢相关脂肪性肝病的最新研究进行综述,以期为临床防治提供新的思路。     

靶向肠道菌群治疗胃肠疾病研究进展

近年来,越来越多的疾病被发现与肠道菌群失调相关,特别是近5年来一些颠覆性的发现使得肠道菌群成为健康、疾病领域的热点问题.作为机体生物过程的重要协调者以及多种疾病发生发展过程中的共同参与者,加之其组成和功能的可塑性,肠道菌群逐渐成为一个极富吸引力的预防和治疗疾病的靶标而引起研究者的高度重视.本文就肠道菌群与肠易激综合征、...     

肠道菌群改变在肝脏疾病中作用的研究进展

肠道菌群改变可能参与了多种肝脏疾病的发生和发展.近年来研究发现,非酒精性脂肪性肝病、酒精性肝病、自身免疫性肝炎、原发性硬化性胆管炎和原发性胆汁性胆管炎等肝脏疾病患者存在肠道菌群的改变.菌群移植及益生菌干预等方法在多种肝脏疾病的治疗中显示出一定的效果.该文就肠道菌群改变在肝脏疾病中的作用,以及肠道菌群调节用于肝脏疾病治疗...     

谷氨酰胺与肠道疾病

谷氨酰胺与肠道疾病屠伟峰黎介寿南京军区南京总医院中国人民解放军普外研究所江苏省南京市２１０００２ＳｕｂｊｅｃｔｈｅａｄｉｎｇｓＧｌｕｔａｍｉｎｅＩｎｔｅｓｔｉｎｅ，ｓｍａｌ／ｔｒａｎｓｐｌａｎｔａｔｉｏｎＳｈｏｒｔｂｏｗｅｌｓｙｎｄｒｏｍｅ／ｔｈ...     

益生菌在肠道疾病治疗中的应用

肠道是人体主要的消化器官,肠道功能的正常与否直接关乎人体健康。益生菌具有调节人体正常菌群和人体免疫的功能,近年来其临床治疗作用越发受到人们的重视。本文介绍益生菌在几种主要肠道疾病治疗中的应用。     

肠道菌群调节在消化系统疾病治疗中的应用

肠道微生态系统对机体正常功能的发挥起至关重要的作用。肠道菌群失调参与人体各系统多种疾病的发病过程,益生菌制剂和粪便菌群移植技术因能有效调节肠道菌群且无明显不良反应而成为当今疾病治疗研究的热点课题。本文就肠道菌群调节在消化系统疾病治疗中的应用情况作一综述。     

肠道微生物在人类疾病中的作用

人类肠道中栖息着上百种微生物,行使着消化、营养、免疫、共生等重要生理功能,大量研究表明肠道微生物对肠道功能具有重要影响。利用系统生物学方法可从整体上研究人体肠道系统,确认肠道微生物与免疫、代谢之间的关联。本文就肠道微生物与人类疾病间的相互作用,包括免疫缺陷相关疾病、腹腔疾病、环境性肠病、肠道细菌相关的代谢疾病和肥胖,以及致病机制和研究模型作一综述。     

肠道菌群对炎症性肠病诊断的研究进展

炎症性肠病(inflammatory bowel disease, IBD)是由免疫、遗传、环境三因素共同作用导致,由于它存在发病早期症状不典型及后期病变多样化的特点,因此在发病早期准确诊断IBD是一个难点,目前诊断依赖于内镜检查和影像学检查,但是患者缺乏依从性.肠道菌群在IBD中的特征性变化提示它可能成为一种新的生物标记物.近年来多项临床研究深入探讨肠道菌群在IBD鉴别诊断、疾病活动度、肠外表现等中的特征性变化,并建立肠道菌群诊断模型,获得了较高的敏感性和特异性,但由于该模型易受外界因素干扰,仍需进一步完善.本文拟将综述肠道菌群对IBD的诊断价值及临床意义.     

脆弱拟杆菌对结直肠疾病的作用以及菌群治疗的展望

脆弱拟杆菌(BF)是人体肠道共生菌,对肠道环境有多种影响。BT可分为肠毒素脆弱拟杆菌(ETBF)和非肠毒素脆弱拟杆菌(NTBF)。ETBF会导致腹泻、结肠炎、炎症性肠病、结直肠癌等结直肠相关疾病,而NTBF对肠道稳态具有保护作用,对其他微生物提供营养支持,同时能增强免疫细胞的抗炎作用。本文就BF对结直肠疾病的影响以及菌群治疗的展望作一综述。     

Akkermansia muciniphila strain ATCC BAA-835 does not promote short-term intestinal inflammation in gnotobiotic interleukin-10-deficient mice

Akkermansia muciniphila is a common member of the intestinal microbiota of healthy human individuals. Its abundance is negatively associated with inflammatory bowel disease and metabolic disorders and the oral administration of A. muciniphila improves the symptoms of metabolic disease in mice. Therefore, A. muciniphila is a promising candidate for the treatment of type-2 diabetes and obesity. However, some studies using animal models of intestinal inflammation reported that A. muciniphila may exacerbate gut inflammation. Because of these contradictory reports the present study aimed to clarify the role of A. muciniphila in the development of intestinal inflammation and the conditions promoting it. For this purpose, the short-term colitogenic potential of A. muciniphila strain ATCC BAA-835 was investigated in colitis-prone, gnotobiotic IL-10-deficient (Il10^-/-) mice. Il10^-/- mice mono-associated with A. muciniphila showed no signs of intestinal inflammation based on body-weight change, histopathological scoring and inflammatory markers. Additional association of the mice with the colitogenic Escherichia coli strain NC101 led to cecal but not colonic inflammation. However, the severity of the inflammation did not exceed that observed in mice mono-associated with E. coli NC101. Il10^-/- mice colonized with a simplified human intestinal microbiota showed increased histopathology, but no increase in inflammatory markers. Furthermore, co-colonization with A. muciniphila did not modify histopathology. The turnover of intestinal mucus was similar in all groups despite the mucus-degrading property of A. muciniphila. Overall, the data do not support a short-term pro-inflammatory effect of A. muciniphila strain ATCC BAA-835 in the Il10^-/- mouse model for inflammatory bowel disease.     

Pasteurized Akkermansia muciniphila increases whole-body energy expenditure and fecal energy excretion in diet-induced obese mice

ABSTRACT

Accumulating evidence points to Akkermansia muciniphila as a novel candidate to prevent or treat obesity-related metabolic disorders. We recently observed, in mice and in humans, that pasteurization of A. muciniphila increases its beneficial effects on metabolism. However, it is currently unknown if the observed beneficial effects on body weight and fat mass gain are due to specific changes in energy expenditure. Therefore, we investigated the effects of pasteurized A. muciniphila on whole-body energy metabolism during high-fat diet feeding by using metabolic chambers. We confirmed that daily oral administration of pasteurized A. muciniphila alleviated diet-induced obesity and decreased food energy efficiency. We found that this effect was associated with an increase in energy expenditure and spontaneous physical activity. Strikingly, we discovered that energy expenditure was enhanced independently from changes in markers of thermogenesis or beiging of the white adipose tissue. However, we found in brown and white adipose tissues that perilipin2, a factor associated with lipid droplet and known to be altered in obesity, was decreased in expression by pasteurized A. muciniphila. Finally, we observed that treatment with pasteurized A. muciniphila increased energy excretion in the feces. Interestingly, we demonstrated that this effect was not due to the modulation of intestinal lipid absorption or chylomicron synthesis but likely involved a reduction of carbohydrates absorption and enhanced intestinal epithelial turnover.

In conclusion, this study further dissects the mechanisms by which pasteurized A. muciniphila reduces body weight and fat mass gain. These data also further support the impact of targeting the gut microbiota by using specific bacteria to control whole-body energy metabolism.     

The protective effect of Bifidobacterium bifidum G9-1 against mucus degradation by Akkermansia muciniphila following small intestine injury caused by a proton pump inhibitor and aspirin

ABSTRACT

Background

Proton pump inhibitors (PPIs) can alleviate upper gastrointestinal injury but paradoxically exacerbate aspirin (ASA)-induced small intestine injury. In this study, our goal was to simulate this exacerbation by developing an appropriate animal model, which may help in establishing treatments. Methods: Male mice were fed a 60% fructose diet for 9 weeks, then administered 200 mg/kg ASA 3 h before sacrifice. The PPI omeprazole was administered intraperitoneally once daily for 9 weeks. Bifidobacterium bifidum G9-1 was administered orally for the last week. In addition, Akkermansia muciniphila was administered orally for 9 weeks instead of omeprazole. Results: ASA-induced small-intestine injury was observed in high-fructose fed mice. Omeprazole exacerbated ASA-induced intestinal damage, significantly decreased Bifidobacteria levels, and significantly increased A. muciniphila counts in the jejunum. The direct administration of A. muciniphila caused thinning of the jejunum mucus layer, which was also observed in mice that received ASA and omeprazole. On the other hand, the administration of Bifidobacterium bifidum G9-1 inhibited A. muciniphila growth and reduced thinning of the mucus layer. The number of goblet cells in the jejunum was reduced by the administration of ASA and omeprazole, while Bifidobacterium bifidum G9-1 prevented the reduction. Conclusions: These results suggest that omeprazole-induced gut dysbiosis promotes Akkermansia growth and inhibits Bifidobacterium growth, leading to a thinning of the mucus layer through a reduction in goblet cells in the small intestine. Probiotics are, therefore, a promising approach for the treatment of small intestine injury.     

肠电刺激对肠运动功能的作用

电刺激通过调节胃肠道动力而发挥特异性治疗消化系疾病的作用,如通过植入刺激系统治疗胃轻瘫。目前肠电刺激在肠动力障碍性疾病中的作用已引起广泛重视,最近有研究发现肠电刺激能有效替代药物和手术而用于肠道动力疾病的治疗。本文就肠电刺激介导的肠动力作用及其临床应用作一综述。     

单气囊小肠镜在小肠疾病诊断中的临床应用

背景:小肠镜的应用使观察完整的小肠成为可能,但目前关于单气囊小肠镜诊断小肠疾病的研究尚较少。目的:评价单气囊小肠镜对小肠疾病的诊断价值、安全性和患者耐受性。方法:对2009年2～9月上海新华医院收治的28例疑似小肠疾病患者行单气囊小肠镜检查,分析疾病检出率、操作相关并发症以及患者的耐受性。结果:本组经口进镜者9例,经肛门进镜17例,分别从两端进镜2例。检查操作时间40～100 min,平均(65.0±25.7)min。插管成功率96.4%。20例患者发现阳性病灶,检出率71.4%。所有患者均未发生操作相关并发症,耐受性良好。结论:单气囊小肠镜是一种对小肠疾病诊断价值较高、安全可靠的检查手段。     

内镜光动力学疗法在食管疾病中的应用

光动力学疗法(PDT)可用于恶性肿瘤及其癌前病变的治疗,主要作用机制为通过产生活性氧簇杀伤肿瘤细胞。目前内镜PDT在食管疾病的治疗中应用较为广泛。本文总结了PDT的基础原理,着重介绍其对Barrett食管伴异型增生和食管癌的疗效、并发症和不良反应,并客观比较了PDT与其他疗法治疗上述食管疾病的优缺点。     

阿克曼氏菌与动脉粥样硬化关系的研究进展

动脉粥样硬化(As)是一种复杂的慢性炎症性疾病,是导致缺血性心脏病和中风在内的心血管疾病(CVD)的主要病因,在世界范围内造成很高的发病率和死亡率。近年来,肠道菌群在As中的作用受到广泛关注。而阿克曼氏菌作为一种重要的抗As作用的有益菌却少有综述。深入探讨As发病机制及潜在治疗方法是当前医学发展的焦点。因此,文章就阿克曼氏菌如何发挥抗As作用及与抗As药物之间的关系予以综述。     

肠道微生态失衡致非酒精性脂肪性肝病发病机制的研究进展

非酒精性脂肪性肝病（NAFLD）已成为一种常见的慢性肝病。近年肠道微生态失衡致NAFLD发病的机制研究已成为一个新的热点。国内外文献已报道相关发病机制可能包括干扰代谢、促进胰岛素抵抗、产生毒性代谢产物、增加肠壁通透性、激活肠道免疫、加重肝脏脂质氧化和氧化应激、激活肝脏免疫炎症损伤和肝纤维化等。而NAFLD发展到一定阶段后又可反过来影响肠道微生态,形成恶性循环。本文就肠道微生态失衡致NAFLD发病机制的研究进展作一综述。