益生菌与肥胖

1、Introduction（gut microbiota ）Ten trillion to 100 trillion (1014) microorganisms populate the adult intestines . The vast majority reside in the colon, where densities approach 10111012 cells/mL. Almost all of these organisms are bacteria, and a minority are archaeons, eukaryotes, and viruses The two

2、 most abundant bacterial phyla in humans and in mice are the Firmicutes (60 80%) and the Bacteroidetes (2040%) The gut microbiota composition depends on age, sex, geography, ethnicity, family, and diet, and can be modulated by prebiotics, probiotics, and antibiotics. M. Million et al.Gut bacterial m

3、icrobiota and obesity.2013Introduction（obesity）The mechanisms by which gut microbiota affect obesity in humans are complicated and largely unknown, the proposed statements may consist of: an excessive bodily energy harvest, higher levels of SCFAs to promote adipogenesis, overexpression of the obesit

4、y-related genes, and increased production of LPS by gut microbiota causing obesity and Inflammation SCFAs increase intestinal absorption of monosaccharides ，modulate host appetite and food intake ，influence lipid metabolism by increas- ing lipogenesis9 and inhibiting fatty acids oxidation Davide Fes

5、ti et al.Gut microbiota and metabolic syndrome.2014Jia Chen et al.Diet Effects in Gut Microbiome and Obesity. 2014 Jia Chen et al.Diet Effects in Gut Microbiome and Obesity. Journal of Food Science r Vol. 79, Nr. 4, 2014 肠道菌群与肥胖肠道菌群与肥胖肠道菌群与肥胖肠道菌群被认为与人类的疾病、健康有着密切的联系。除了对胃肠道功能的影响，还涉及肝脏、大脑、脂肪组织等。目前新的研究认

6、为肠道菌群与肥胖有着密切的联系。肥胖人群的与正常人群相比，除能量代谢不平衡，在肠道菌群的组成上也存在差异。据说肥胖与肠道中两种菌（厚壁菌拟杆菌）的比例相关。Tulika Arora et al.Probiotics: Interaction with gut microbiome and antiobesity potential.2013 肠道菌群与肥胖12名名obese adults随机分为随机分为2组，分别给予组，分别给予low-fat、low-CHO饮食饮食1年；与年；与lean adults（normal weight）相比，这些）相比，这些obese adults肠道中拟杆肠道中拟

7、杆菌菌（Bacteroidetes）数量少，厚壁菌拟杆菌（）数量少，厚壁菌拟杆菌（ratio of FirmicutesBacteroidetes ）比值更高；）比值更高；lean adults减肥成功后，比值回到正常水平减肥成功后，比值回到正常水平25 overweight or obese 与24 normal weight children相比，双歧杆菌含量更低，金黄色葡萄球菌的含量更高Marina Sanchez et al.Childhood Obesity: A Role for Gut Microbiota?2015 肥胖人群在肠道菌群的组成上与正常人存在差异肥胖人群在肠道菌群的

8、组成上与正常人存在差异 肠道菌群与肥胖围产期益生菌干预对胎儿体重增长10年的观察研究159名孕妇随机分成2组，在预产期前4周及产后6个月分别给予乳酸菌和麦芽糊精，结果显示，这种早期的益生菌干预能预防胎儿过多的体重增加母亲的肠道菌群影响胎儿肠道菌群，早期益生菌调母亲的肠道菌群影响胎儿肠道菌群，早期益生菌调节能预防胎儿过多的体重增加节能预防胎儿过多的体重增加Marina Sanchez et al.Childhood Obesity: A Role for Gut Microbiota?2015 ？影响肠道菌群影响肠道菌群不同国家饮食习惯存在差异，肠道菌群的组成也有差异。美国人肠道中厚壁菌水平高，

9、日本人肠道中放线菌水平高，韩国人和中国人肠道中拟杆菌水平高。plant-rich diet与low-fiber diet相比，前者厚壁菌水平更低，后者肠杆菌（志贺氏杆菌、埃希氏杆菌）水平更高vegetarian diet 与Western diet 相比，前者肠道中以Clostridium coccoides，Clostridium ramosum 为主，缺少Faecalibacterium prausnitzii. 饮食与肠道菌群Nam Y-D et al. Comparative analysis of Korean human gut microbiota by barcoded pyr

10、osequencing .2011 肠壁的通透性高脂饮食改变改变肠道菌群的组成，并改变某些紧密结合蛋白（tight junction proteins，ZO-1 and occludin ）的分布，影响肠道的通透性肠壁通透性增加使血液中LPS（细菌内毒素）增加，LPS与TLR4/CD14 受体结合，促进TNF-、 IL-6的释放，增加动脉粥样硬化、肥胖、胰岛素抵抗的风险。肠道菌群的改变刺激CB1 receptors ，激活内源性大麻素系统（endocannabinoid system），增加肠道的通透性，刺激脂肪生成；通过抑制PPAR molecules 刺激脂肪生成肠道菌群失调减少肌肉和肝脏

11、中AMPK，减少脂肪氧化，增加脂肪生成Marina Sanchez et al.Childhood Obesity: A Role for Gut Microbiota?2015 激素与肠道菌群肠道菌群的改变影响胃肠激素GLP-1、PYY、ghrelin （胃饥饿素）的分泌，这些激素影响血糖的调节、饱腹感和能量的摄入。补充益生元能抑制GLP-1、PYY，增加ghrelin分泌，抑制胃肠动力延缓胃排空。肠道菌群紊乱减少FIAF protein （an inhibitor of lipoprotein lipase ，LPL）的表达，增加LPL（脂蛋白脂肪酶）活性 ，增加脂肪的存储Marina S

12、anchez et al.Childhood Obesity: A Role for Gut Microbiota?2015 Figure 1. Dysbiosis in the gut microbiota may lead to obesity via different mechanisms. (A) An imbalance in intestinal microbiota leads to an increase in SCFA and gut permeability and decrease in FIAF and AMPK; and (B) A restored microbi

13、ota by prebiotics and/or probiotics may inhibit the mechanisms described in (A) and lead to an increase in the hormones PYY and GLP-1 and decrease in ghrelin. 益生菌调节肠道菌群Marina Sanchez et al.Childhood Obesity: A Role for Gut Microbiota?2015 益生菌与体重控制益生菌与体重控制相关研究（1）one study investigating the effect of

14、consuming VLS3, a combination of eight probiotic strains, for four months on non-alcoholic fatty liver disease in 48 children, found a significant increase in GLP-1 concentrations and reduction in BMI compared to placebo （2）dairy beverages fermented with L. acidophilus and Proprionibacterium freuden

15、reichii increased satiety compared with a non-fermented dairy beverage in healthy normal weight female individuals （3）In a study examining the effect of a formulation of probiotics (Lactobacillus rhamnosus) and prebiotics (oligofructose + inulin) and maltodextrin placebo on weight loss over 24 weeks

16、 in 126 obese individuals, it was found that women consuming the formulation lost approximately twice the weight than women consuming the placebo 相关研究（4）In a randomized, controlled intervention, 87 healthy overweight adults consuming fermented milk containing Lactobacillus gasseri SBT2055 (200 g/day

17、) for 12 weeks reduced their visceral and subcutaneous fat, body weight and BMI compared with the control group. （5）Bervoets et al. recently investigated the gut microbiota of 26 overweight/obese and 27 lean children and found that obese children had a higher ratio of Firmicutes/Bacteroidetes （6）In

18、another study, fecal samples were analyzed in 15 obese and 15 normal weight children to compare differences in the gut bacterial community . Significantly higher concentrations of the SCFA, butyrate and propionate, and significantly lower concentrations of intermediate metabolites in obese children were observed compared to those with normal weight. 参考文献(1)M. Million et al.Gut bacterial microbiota and obesity.2013(2)Davide Festi et al.Gut microbiota and metabolic