肠道菌群与代谢疾病.ppt

肠道菌群与代谢疾病,目录,肠道菌群与健康和疾病概述 肠-脑轴 肠-肝轴 肠道菌群与代谢性疾病：肥胖、糖尿病 肠道菌群与肠病 肠道菌群与免疫 肠道菌群与其它疾病 革命带来的挑战和机遇,悄悄发生的革命,INNA SEKIROV, et al., Gut Microbiota in Health and Disease. Physiol Rev 90: 859904, 2010;,一篇值得关注的综述,Nature reviews. Microbiology 最新的影响因子为22.490 (2013),人菌共生,Kristina Harris,et al., Is the GutMicrobiota a New Factor Contributing to Obesity and ItsMetabolic Disorders? Journal of Obesity, Volume 2012, p 1-14.,人肠道菌群种类和数量,EAMONN M. M. QUIGLEY and RODRIGO QUERA, Small Intestinal Bacterial Overgrowth: Roles of Antibiotics, Prebiotics, and Probiotics. GASTROENTEROLOGY 2006;130:S78S90,好细菌和坏细菌,菌群是健康的核心,Nathalie M. Delzenne, et al., Targeting gut microbiota in obesity: effects of prebiotics and probiotics. Nat. Rev. Endocrinol. 7, 639646 (2011).,肠道菌群对人生理的影响,肠道菌群-代谢产物-功能,Jeremy K. Nicholson et al., Host-Gut Microbiota Metabolic. Science 336, 1262-1267, 2012.,影响肠道菌群的因素,Nathalie M. Delzenne & Patrice D. Cani, Interaction Between Obesity and the Gut Microbiota: Relevance in Nutrition. Annu. Rev. Nutr. 2011. 31:1531.,影响肠道菌群的因素,肠-脑轴/脑-肠轴,Germ Free (GF) Mice Display Increased Motor Activity and Reduced Anxiety-Like Behavior. results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior.,肠-脑轴的概念,Augusto J. Montiel-Castro, et al., The microbiotagutrainaxis: neurobehavioral correlates, healthand sociality. Front in Integ Neuro. Oct 2013 | Vol7 | Article 70 | 1-16.,脑-肠轴/肠-脑轴：迷走神经,Sue Grenham,et al., Braingutmicrobe communication in health and disease. Frontiers in Physio. Gastroint Sci Dec 2011 Vol 2 p 1-15.,肠脑轴/脑肠轴,Q. AZIZ, et al., Gut microbiota and gastrointestinal health: current concepts and future directions. Neurogastroenterol Motil (2013) 25, 415.,菌群影响神经功能,Eamonn M.M. Quigley. Do patients with functional gastrointestinal disorders have an altered gut flora? Ther Adv Gastroenterol (2009) 2(Suppl 1) S23S30.,菌群紊乱致焦虑和抑郁,Jane A. Foster and Karen-Anne McVey Neufeld, Gutbrain axis: how the microbiome influences anxiety and depression. Trends in Neurosciences, May 2013, Vol. 36, No. 5, P 305-312,精神活动影响肠道菌群,Jason A. Hawrelak 9(2):180-197.,exposure to psychological stress results in a significant reduction in the production of mucin and a decreased presence of acidic mucopolysaccharides on the mucosal surface.,应激/压力引起胃肠疾病,P.C. KONTUREK, et al., STRESS AND THE GUT: PATHOPHYSIOLOGY, CLINICAL CONSEQUENCES, DIAGNOSTIC APPROACH AND TREATMENT OPTIONS. J PHYSIO & PHARM 2011, 62, 6, 591-599.,脑肠轴紊乱导致溃疡,P.C. KONTUREK, et al., STRESS AND THE GUT: PATHOPHYSIOLOGY, CLINICAL CONSEQUENCES, DIAGNOSTIC APPROACH AND TREATMENT OPTIONS. J PHYSIO & PHARM 2011, 62, 6, 591-599.,应激导致IBD,P.C. KONTUREK, et al., STRESS AND THE GUT: PATHOPHYSIOLOGY, CLINICAL CONSEQUENCES, DIAGNOSTIC APPROACH AND TREATMENT OPTIONS. J PHYSIO & PHARM 2011, 62, 6, 591-599.,应激导致IBS,P.C. KONTUREK, et al., STRESS AND THE GUT: PATHOPHYSIOLOGY, CLINICAL CONSEQUENCES, DIAGNOSTIC APPROACH AND TREATMENT OPTIONS. J PHYSIO & PHARM 2011, 62, 6, 591-599.,慢性疲劳与肠-脑轴,肠道菌群和自闭症,GI barrier defects and microbiota alterations in the maternal immune activation (MIA) mouse model that is known to display features of ASD. Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition, and ameliorates defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. autism, and likely other behavioral conditions, are potentially diseases involving the gut that ultimately impact the immune, metabolic, and nervous systems, and that microbiome-mediated therapies may be a safe and effective treatment for these neurodevelopmental disorders. these findings support a gut-microbiome-brain connection in a mouse model of ASD and identify a potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders.,Elaine Y. Hsiao, et al., Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders. Cell 155, 14511463,肠-脑轴和自闭症,Caroline G.M. de Theije, et al., Pathways underlying the gut-to-brain connection in autism spectrum disorders as future targets for disease management. European Journal of Pharmacology 668 (2011) S70S80,肠-肝轴,Eamonn M. M. Quigley, Gut Bacteria in Health and Disease. Gastro & Hepat Vol 9, 9, 2013, P 560-569.,1998年马歇尔提出了“肠-肝轴”的概念,对肠道和肝脏功能关系的认识提示新的治疗理念,为肠道和肝脏疾病的治疗探寻新的治疗靶点。,肠-肝轴之间的互动 肠道菌群失调，大量G-杆菌繁殖,LPS产生显著增多肠粘膜屏障功能受损,致病菌和LPS大量移位，经门静脉入肝，损害肝功能。,肝功能异常KCs代谢和清除LPS降低，导致肠道功能异常,Gakuhei Son, et al., Contribution of Gut Bacteria to Liver Pathobiology. Gastroe Res and Prac, Vol 2010, Article ID 453563, 13 pages.,肠肝对话,肠道菌群致非酒精性脂肪肝,Valentina Tremaroli & Fredrik Bckhed, Functional interactions between the gut microbiota and host metabolism. NATURE | VOL 489 | 13 SEPTEMBER 2012,肠道菌群导致脂肪肝,Carmine Finelli and Giovanni Tarantino, NONALCOHOLIC FATTY LIVER DISEASE, DIET AND GUT MICROBIOTA. EXCLI Journal 2014;13:461-490,肝脏疾病和SIBO,肠道菌群与代谢性疾病,肠道菌群增加能量储存,Nathalie M. Delzenne & Patrice D. Cani, Interaction Between Obesity and the Gut Microbiota: Relevance in Nutrition. Annu. Rev. Nutr. 2011. 31:1531.,肠道菌群导致能量聚集,Patrice D Cani and Nathalie M Delzenne, Interplay between obesity and associated metabolic disorders: new insights into the gut microbiota. Current Opinion in Pharmacology 2009, 9:737743.,肠道菌群引发多种代谢疾病,肠道菌群和肥胖,肠道菌群和肥胖是一个新的热门话题,肥胖的定义,肥胖病一般被定义作为有 BMI 30 以上。,体重将近900磅(约400公斤)的里基(Ricky Naputi)现年39岁，是世界最重的男子之一。因为体型过于笨重而难以移动，他已经在坐落于太平洋关岛的家中躺了五年之久。,肥胖和正常人,Amandine Everard & Patrice D. Cani, Diabetes, obesity and gut microbiota. Best Practice & Research Clinical Gastroenterology 27 (2013) 7383.,史氏甲烷短杆菌和肥胖,为了确定肠道菌群的改变和验证人体肠道中的乳杆菌或双歧杆菌是否与肥胖或消瘦相关，我们采用定量PCR和乳杆菌选择性培养基分析了68位肥胖志愿者和47位对照的粪便菌群中硬壁菌、拟杆菌、乳酸乳球菌、动物双歧杆菌和若干乳杆菌种的数量。 结果：定量PCR试验中，动物双歧杆菌(OR=0.63; 95% CI 0.39-1.01; P=0.056)和史氏甲烷短杆菌(OR=0.76; 95% CI 0.59-0.97; P=0.03)与正常体重相关，而罗伊氏乳杆菌(OR=1.79; 95% CI 1.03-3.10; P=0.04)与肥胖相关。,Million M, et al., Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii.Int J Obes (Lond). 2011 Aug 9.,产甲烷肥胖的人有较高的身体质量指数,58人，BMI显着较高的甲烷阳性者（45.22.3公斤/米2）比甲烷阴性（38.50.8公斤/米2，P= 0.001）。甲烷阳性者也有更大程度的便秘与甲烷相比，阴性者（21.36.4比9.52.4，P?= .043）。多元回归分析说明了BMI甲烷之间有显着的关系。 结论：这是人类第一次有研究表明，较高浓度的甲烷检测呼气测试是预测显着更大的肥胖超重者。,B.Basseri等，肝脏病杂志胃肠病学杂志，2012年1月8（1）：22-28,美国Cedars-Sinai 医学中心,肠道菌群致肥胖原因,Valentina Tremaroli & Fredrik Bckhed, Functional interactions between the gut microbiota and host metabolism. NATURE | VOL 489 | 13 SEPTEMBER 2012,肠道菌群致肥胖原理,JOHN K. DIBAISE, et al., Gut Microbiota and Its Possible Relationship With Obesity. Mayo Clin Proc. 2008;83(4):460-469.,不同胖瘦人群肠道菌群数量,Fabrice Armougom, et al., Monitoring Bacterial Community of Human Gut Microbiota Reveals an Increase in Lactobacillus in Obese Patients and Methanogens in Anorexic Patients. PLoS ONE 4(9): e7125.,肠道菌群和糖尿病,肠道菌群和I型糖尿病,肠道菌群和I型糖尿病,肠道菌群和II型糖尿病,Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and stablished the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.,Junjie Qin, et al., A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 5560 (04 October 2012),肠道菌群和II型糖尿病,Junjie Qin, et al., A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 5560 (04 October 2012),菌群紊乱导致炎症,June L. Round and Sarkis K. Mazmanian. The gut microbiota shapes intestinal immune responses during health and disease. NATURE REVIEWS | IMMUNOLOGY, VOLUME 9 | MAY 2009 | 313-324.,肠道菌群紊乱引发的免疫疾病,肠道菌群紊乱导致过敏和炎症,肠粘膜屏障损伤导致炎症,Silvio Balzan, et al., Bacterial translocation: Overview of mechanisms and clinical impact. J Gastro & Hepat 22 (2007) 464471.,IBD发生机制,Eamonn M. M. Quigley, Gut Bacteria in Health and Disease. Gastro & Hepat Vol 9, 9, 2013, P 560-569.,致病菌导致IBD,INNA SEKIROV,