腸道菌群與代謝疾病,目錄,腸道菌群與健康和疾病概述 腸-腦軸 腸-肝軸 腸道菌群與代謝性疾病：肥胖、糖尿病 腸道菌群與腸病 腸道菌群與免疫 腸道菌群與其它疾病 革命帶來的挑戰和機遇,悄悄發生的革命,INNA SEKIROV, et al., Gut Microbiota in Health and Disease. Physiol Rev 90: 859904, 2010;,一篇值得關注的綜述,Nature reviews. Microbiology 最新的影響因子為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.,人腸道菌群種類和數量,EAMONN M. M. QUIGLEY and RODRIGO QUERA, Small Intestinal Bacterial Overgrowth: Roles of Antibiotics, Prebiotics, and Probiotics. GASTROENTEROLOGY 2006;130:S78S90,好細菌和壞細菌,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).,腸道菌群對人生理的影響,腸道菌群-代謝產物-功能,Jeremy K. Nicholson et al., Host-Gut Microbiota Metabolic. Science 336, 1262-1267, 2012.,影響腸道菌群的因素,Nathalie M. Delzenne & Patrice D. Cani, Interaction Between Obesity and the Gut Microbiota: Relevance in Nutrition. Annu. Rev. Nutr. 2011. 31:1531.,影響腸道菌群的因素,腸-腦軸/腦-腸軸,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.,腸-腦軸的概念,Augusto J. Montiel-Castro, et al., The microbiotagutrainaxis: neurobehavioral correlates, healthand sociality. Front in Integ Neuro. Oct 2013 | Vol7 | Article 70 | 1-16.,腦-腸軸/腸-腦軸：迷走神經,Sue Grenham,et al., Braingutmicrobe communication in health and disease. Frontiers in Physio. Gastroint Sci Dec 2011 Vol 2 p 1-15.,腸腦軸/腦腸軸,Q. AZIZ, et al., Gut microbiota and gastrointestinal health: current concepts and future directions. Neurogastroenterol Motil (2013) 25, 415.,菌群影響神經功能,Eamonn M.M. Quigley. Do patients with functional gastrointestinal disorders have an altered gut flora? Ther Adv Gastroenterol (2009) 2(Suppl 1) S23S30.,菌群紊亂致焦慮和抑郁,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,精神活動影響腸道菌群,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.,應激/壓力引起胃腸疾病,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.,腦腸軸紊亂導致潰瘍,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.,應激導致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.,應激導致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.,慢性疲勞與腸-腦軸,腸道菌群和自閉癥,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,腸-腦軸和自閉癥,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,腸-肝軸,Eamonn M. M. Quigley, Gut Bacteria in Health and Disease. Gastro & Hepat Vol 9, 9, 2013, P 560-569.,1998年馬歇爾提出了“腸-肝軸”的概念,對腸道和肝臟功能關系的認識提示新的治療理念,為腸道和肝臟疾病的治療探尋新的治療靶點。,腸-肝軸之間的互動 腸道菌群失調，大量G-桿菌繁殖,LPS產生顯著增多腸粘膜屏障功能受損,致病菌和LPS大量移位，經門靜脈入肝，損害肝功能。,肝功能異常KCs代謝和清除LPS降低，導致腸道功能異常,Gakuhei Son, et al., Contribution of Gut Bacteria to Liver Pathobiology. Gastroe Res and Prac, Vol 2010, Article ID 453563, 13 pages.,腸肝對話,腸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,腸道菌群導致脂肪肝,Carmine Finelli and Giovanni Tarantino, NONALCOHOLIC FATTY LIVER DISEASE, DIET AND GUT MICROBIOTA. EXCLI Journal 2014;13:461-490,肝臟疾病和SIBO,腸道菌群與代謝性疾病,腸道菌群增加能量儲存,Nathalie M. Delzenne & Patrice D. Cani, Interaction Between Obesity and the Gut Microbiota: Relevance in Nutrition. Annu. Rev. Nutr. 2011. 31:1531.,腸道菌群導致能量聚集,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.,腸道菌群引發多種代謝疾病,腸道菌群和肥胖,腸道菌群和肥胖是一個新的熱門話題,肥胖的定義,肥胖病一般被定義作為有 BMI 30 以上。,體重將近900磅(約400公斤)的里基(Ricky Naputi)現年39歲，是世界最重的男子之一。因為體型過于笨重而難以移動，他已經在坐落于太平洋關島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.,史氏甲烷短桿菌和肥胖,為了確定腸道菌群的改變和驗證人體腸道中的乳桿菌或雙歧桿菌是否與肥胖或消瘦相關，我們采用定量PCR和乳桿菌選擇性培養基分析了68位肥胖志愿者和47位對照的糞便菌群中硬壁菌、擬桿菌、乳酸乳球菌、動物雙歧桿菌和若干乳桿菌種的數量。 結果：定量PCR試驗中，動物雙歧桿菌(OR=0.63; 95% CI 0.39-1.01; P=0.056)和史氏甲烷短桿菌(OR=0.76; 95% CI 0.59-0.97; P=0.03)與正常體重相關，而羅伊氏乳桿菌(OR=1.79; 95% CI 1.03-3.10; P=0.04)與肥胖相關。,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.,產甲烷肥胖的人有較高的身體質量指數,58人，BMI顯著較高的甲烷陽性者（45.22.3公斤/米2）比甲烷陰性（38.50.8公斤/米2，P= 0.001）。甲烷陽性者也有更大程度的便秘與甲烷相比，陰性者（21.36.4比9.52.4，P?= .043）。多元回歸分析說明了BMI甲烷之間有顯著的關系。 結論：這是人類第一次有研究表明，較高濃度的甲烷檢測呼氣測試是預測顯著更大的肥胖超重者。,B.Basseri等，肝臟病雜志胃腸病學雜志，2012年1月8（1）：22-28,美國Cedars-Sinai 醫學中心,腸道菌群致肥胖原因,Valentina Tremaroli & Fredrik Bckhed, Functional interactions between the gut microbiota and host metabolism. NATURE | VOL 489 | 13 SEPTEMBER 2012,腸道菌群致肥胖原理,JOHN K. DIBAISE, et al., Gut Microbiota and Its Possible Relationship With Obesity. Mayo Clin Proc. 2008;83(4):460-469.,不同胖瘦人群腸道菌群數量,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.,腸道菌群和糖尿病,腸道菌群和I型糖尿病,腸道菌群和I型糖尿病,腸道菌群和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),腸道菌群和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),菌群紊亂導致炎癥,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.,腸道菌群紊亂引發的免疫疾病,腸道菌群紊亂導致過敏和炎癥,腸粘膜屏障損傷導致炎癥,Silvio Balzan, et al., Bacterial translocation: Overview of mechanisms and clinical im