Gut Microbiota and Obesity Gut Microbiota and Obesity Gut - - PowerPoint PPT Presentation

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Gut Microbiota and Obesity Gut Microbiota and Obesity Gut Microbiota and Obesity Gut Microbiota and Obesity

高贵喜 2010.5. 2010.5. 2010.5. 2010.5.

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backgroud backgroud backgroud backgroud

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hypertension hypertension hypertension hypertension

NAFLD NAFLD NAFLD NAFLD

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Ⅱdiabetes diabetes diabetes diabetes cardiovascular cardiovascular cardiovascular cardiovascular disease disease disease disease

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Obesity and associated Obesity and associated Obesity and associated Obesity and associated metabolic disorders metabolic disorders metabolic disorders metabolic disorders.

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Diagram Diagram Diagram Diagram

heredity status heredity status heredity status heredity status

nutrition nutrition nutrition nutrition

Lifestyle Lifestyle Lifestyle Lifestyle

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microbiota microbiota microbiota microbiota

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Formation of microbiota Formation of microbiota Formation of microbiota Formation of microbiota

sterile sterile sterile sterile amniotic amniotic amniotic amniotic fluid fluid fluid fluid

birth cana birth cana birth cana birth canal

food, beverags the environment m e d i c i n e 、 d i s e a s e 、 M e t a b

• l

i s m 、 i m m u n e

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microbiota associated with obesity microbiota associated with obesity microbiota associated with obesity microbiota associated with obesity

Obese people has more Bacteroidetes than thin people but less Firmicutes. The divisity of microbiota in obese individual is reduced.

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Influence on weight Influence on weight Influence on weight Influence on weight

Jeffery Gordon

• ne third more food

BUT 40 percent less body fat

gain weight though they weren't eating any extra food greater gains in body fat than transplanting gut microbes from normal mice

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2/3 Firmicutes 2/3 Firmicutes 2/3 Firmicutes 2/3 Firmicutes 1/3 Bacteroidetes 1/3 Bacteroidetes 1/3 Bacteroidetes 1/3 Bacteroidetes high-tech DNA sequencers more more more more Firmicutes Firmicutes Firmicutes Firmicutes and many and many and many and many fewer fewer fewer fewer Bacteroidetes Bacteroidetes Bacteroidetes Bacteroidetes

more genes for breaking down complex starches and fiber

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Does this apply to humans? Does this apply to humans? Does this apply to humans? Does this apply to humans?

follow a low-fat or low- follow a low-fat or low- follow a low-fat or low- follow a low-fat or low- carbohydrate diet for a carbohydrate diet for a carbohydrate diet for a carbohydrate diet for a year year year year

a remarkable shift in microbiota

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result result result result

The dynamic linkage between adiposity and gut microbial ecology described here, together with our results from mice 4, indicates that manipulation

• f gut microbial

communities could be another approach in the treatment of obesity.

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reduced divisity of microbiota in obesity reduced divisity of microbiota in obesity reduced divisity of microbiota in obesity reduced divisity of microbiota in obesity

HOW to inflect the weight? HOW to inflect the weight? HOW to inflect the weight? HOW to inflect the weight?

Energy harvest Energy harvest Energy harvest Energy harvest

1 2 3

Affect the inflammatory response Affect the inflammatory response Affect the inflammatory response Affect the inflammatory response regulate the host fat metabolism regulate the host fat metabolism regulate the host fat metabolism regulate the host fat metabolism

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energy harvest: energy harvest: energy harvest: energy harvest: digest non digestible polysaccharides (fermentation of resistant starch,

• ligosaccharides, inulin).

contribute ~10% of the daily energy in take in man. germ free mice had a lower monosaccharide uptake from the intestine to the portal blood. This could be partly explained by the lower capillary density of the small intestine of germ free mice as compared to their conventionalized counterparts。

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Influence on Influence on Influence on Influence on lipornetabolism lipornetabolism lipornetabolism lipornetabolism

Increase the expression of ChREBP/SREBP supress the expression of Fiaf. reduce the activity of AMPK

lipornetabolism

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backhed backhed backhed backhed研究及解释: : : :

normal mice 植入菌群的小鼠 ChREBP SREBP

Acc1 Fas

aceyl-CoA carboxylase fatty acid synthase germ-free mice a two-fold increase in hepatic triglyceride content.low levels of hepatic ChREBP and SREBP-1 mRNA

fasting-inducedfacto fasting-inducedfacto fasting-inducedfacto fasting-inducedfactor

lipoprotein lipoprotein lipoprotein lipoprotein lipase lipase lipase lipase

catalyze the release

• f fatty acids and

triacylglycerol to

• xidate.

Fiaf

normal mice germ-free mice Fiaf-KO mice

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AMP-activated protein kinase (AMPK)

supress the activity of ATPK supress the activity of ATPK supress the activity of ATPK supress the activity of ATPK

phosphorylation of its specific target acetylCoA carboxylase (ACC) no production of malonyl CoA This drop in malonyCoA increases carnitine palmitoyl transferase-1 (CPT-1) promotes mitochondrial fatty acid oxidation Function of AMPK

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AMPK activity AMPK activity AMPK activity AMPK activity

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Obesity as an in Obesity as an in Obesity as an in Obesity as an infm fm fm fmammatory disease ammatory disease ammatory disease ammatory disease

Obesity is associated with a low-grade chronic infmammation which has been implicated in the development of the metabolic syndrome and insulin resistance. High-fat-diet-induced obesity and metabolic disorders are associated with an increased expression of several inflammatory related factors IL-1, TNF- , MCP-1, and IL-6 in muscle, liver and adipose tissue。

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LPS LPS LPS LPS

LPS is a constituent of Gram negative bacteria present in the gut mi-crobiota, LPS triggers the secretion of proinflammatory cytokines when it binds to the complex of CD14 and the toll-like receptor 4 (TLR4) at the surface of innate immune cells LPS is continuously produced within the gut by the death of Gram negative bacteria and is physiologically carried into intestinal capillaries through a TLR4 dependent mechanism LPS is transported from the intestine towards target tissues by a mechanism facilitated by lipoproteins, notably chylomicrons freshly synthesized from epithelial intestinal cells in response to fat feeding.

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LPS LPS LPS LPS

increased whole body, liver and adipose tissue weight, fasting glycaemia and insulinaemia CD14-decient mice

LPS LPS LPS LPS

high fat diet

FAT FAT FAT FAT

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CD14-decient mice

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Conclusion: Conclusion: Conclusion: Conclusion:

人体内的低度、全身性的慢性炎症主要是肠道菌 群结构失调引起的。如果长期大量进食动物性食 品，就会促进条件致病菌的生长，升高肠道内的 抗原量，减少保护肠屏障功能的有益菌，造成肠 壁通透性增加，刺激免疫系统并导致全身发炎。 双歧杆菌提高肠道的渗透性，减少代谢毒素的吸 收。 合理膳食，补充益生菌，维持肠道菌群平衡。

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Referrence: Referrence: Referrence: Referrence:

• Ley RE,Bäckhed F,Turnbaugh P,Lozupone CA,Knight RD,Gordon JI.Obesity alters

gut microbial ecology.Proc Natl Acad Sci USA2005; 102:11070–5.

• Turn baugh PJ,Hamady M,Yatsunenko T etal.A core gut microbiome in obese and

lean twins.Nature 2009; 457:480–4.

• Ley RE,Turnbaugh PJ,Klein S,Gordon JI.Microbial ecology: human gut microbes

associated with obesity.Nature 2006;444:1022–3.

• Cani,P.D.,Amar,J.,Iglesias,M.A.,Poggi,M.,Knauf,C.,Bastelica,D.,etal..Metabolic

endotoxemia initiates obesity and insulin resistance. Diabetes,2007,56,1761–1772.

• Cani,P.D.,&Delzenne,N.M.(2009).The role of the gut microbiota in energy

metabolism and metabolic disease. CurrentPharmaceuticalDesign,15,1546–1558.

• 肠道菌群在肥胖及相关代谢性疾病发生发展中的地位和作用。（张晨虹、赵立平）
• The Fasting-induced Adipose Factor/Angiopoietin-like Protein 4Is Physically

Associated with Lipoprote in sand Governs Plasma Lipid Level sand Adiposity （Received for publication,June 15, 2005, and inrevisd form, September16, 2005 Published,JBCPapers in Press, November4, 2005, DOI10.1074/jbc. M506519200 ）。

• 肥胖与肠道菌群的相关性。（刘伟伟 严 敏）