肠道菌群与代谢疾病肠道菌群与代谢疾病1优质资料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2优质资料悄悄发生的革命INNA SEKIROV, et al., Gut Microbiota in Health and Disease. Physiol Rev 90: 859904, 2010;3优质资料一篇值得关注的综述Nature reviews. Microbiology 最新的影响因子为最新的影响因子为22.490 (2013)4优质资料人菌共生Kristina Harris,et al., Is the GutMicrobiota a New Factor Contributing to Obesity and ItsMetabolic Disorders? Journal of Obesity, Volume 2012, p 1-14.5优质资料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:S78S906优质资料好细菌和坏细菌7优质资料菌群是健康的核心Nathalie M. Delzenne, et al., Targeting gut microbiota in obesity: effects of prebiotics and probiotics. Nat. Rev. Endocrinol. 7, 639646 (2011).8优质资料肠道菌群对人生理的影响9优质资料肠道菌群-代谢产物-功能Jeremy K. Nicholson et al., Host-Gut Microbiota Metabolic. Science 336, 1262-1267, 2012.10优质资料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. 31:15 31.11优质资料影响肠道菌群的因素12优质资料肠-脑轴/脑-肠轴13优质资料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.14优质资料肠-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 | 1-16.15优质资料脑-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 1-15.16优质资料肠脑轴/脑肠轴Q. AZIZ, et al., Gut microbiota and gastrointestinal health: current concepts and future directions. Neurogastroenterol Motil (2013) 25, 415.17优质资料菌群影响神经功能Eamonn M.M. Quigley. Do patients with functional gastrointestinal disorders have an altered gut flora? Ther Adv Gastroenterol (2009) 2(Suppl 1) S23S30.18优质资料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 305-31219优质资料精神活动影响肠道菌群Jason A. Hawrelak & Stephen P. Myers, The Causes of Intestinal Dysbiosis: A Review. Altern Med Rev 2004;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.20优质资料应激/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, 591-599.21优质资料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, 591-599.22优质资料应激导致IBDP.C. KONTUREK, et al., STRESS AND THE GUT: PATHOPHYSIOLOGY, CLINICAL CONSEQUENCES, DIAGNOSTIC APPROACH AND TREATMENT OPTIONS. J PHYSIO & PHARM 2011, 62, 6, 591-599.23优质资料应激导致IBSP.C. KONTUREK, et al., STRESS AND THE GUT: PATHOPHYSIOLOGY, CLINICAL CONSEQUENCES, DIAGNOSTIC APPROACH AND TREATMENT OPTIONS. J PHYSIO & PHARM 2011, 62, 6, 591-599.24优质资料慢性疲劳与肠-脑轴25优质资料26优质资料肠道菌群和自闭症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, 14511463,27优质资料肠-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) S70S8028优质资料肠-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。29优质资料肠肠- -肝轴肝轴之间的互动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.30优质资料肠肝对话31优质资料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 201232优质资料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;13:461-49033优质资料肝脏疾病和SIBO34优质资料肠道菌群与代谢性疾病35优质资料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. 31:15 31.36优质资料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, 9:737743.37优质资料肠道菌群引发多种代谢疾病38优质资料39优质资料40优质资料肠道菌群和肥胖41优质资料肠道菌群和肥胖是一个新的热门话题42优质资料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。43优质资料肥胖和正常人Amandine Everard & Patrice D. Cani, Diabetes, obesity and gut microbiota. Best Practice & Research Clinical Gastroenterology 27 (2013) 7383.44优质资料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 9.45优质资料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46优质资料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 201247优质资料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):460-469.48优质资料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): e7125.49优质资料肠道菌群和糖尿病50优质资料肠道菌群和I型糖尿病51优质资料肠道菌群和I型糖尿病52优质资料肠道菌群和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)53优质资料肠道菌群和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)54优质资料菌群紊乱导致炎症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 | 313-324.55优质资料肠道菌群紊乱引发的免疫疾病56优质资料肠道菌群紊乱导致过敏和炎症57优质资料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) 464471.58优质资料IBD发生机制Eamonn M. M. Quigley, Gut Bacteria in Health and Disease. Gastro & Hepat Vol 9, 9, 2013, P 560-569.59优质资料致病菌导致IBDINNA SEKIROV, et al., Gut Microbiota in Health and Disease. Physiol Rev 90: 859904, 2010;60优质资料SIBO导致肠病INNA SEKIROV, et al., Gut Microbiota in Health and Disease. Physiol Rev 90: 859904, 2010;61优质资料肠道菌群对血管疾病的影响Kristina Harris,et al., Is the GutMicrobiota a New Factor Contributing to Obesity and ItsMetabolic Disorders? Journal of Obesity, Volume 2012, p 1-14.62优质资料肠道菌群致动脉粥样硬化R. Caesar, et al., Effects of gut microbiota on obesity and atherosclerosis via modulation of inflammation and lipid metabolism. J Intern Med 2010; 268: 320328.63优质资料肠道菌群致癌INNA SEKIROV, et al., Gut Microbiota in Health and Disease. Physiol Rev 90: 859904, 2010;64优质资料细菌对免疫和干细胞活动Won-Jae Lee. Bacterial-modulated host immunity and stem cell activation for gut homeostasis. GENES & DEVELOPMENT 23:2260226565优质资料革命带来的机遇如何应对悄然而来的革命66优质资料调节肠道菌群的方法67优质资料Thank YouThank You！68优质资料