史氏产甲烷短杆菌对儿童肥胖发生发展的影响研究

The problem of childhood obesity is deteriorating day by day, and its pathogenesis and related factors are needed to be further studied urgently. Gut microbiota and obesity are closely related, of which methanogenic bacteria is thought to have an effect on the development of overweight and obesity, but further research is needed to be done. Based on our previous found in children cohort study that certain bacteria may be acted as a key bacteria to the development of obesity. We intend to isolate and identify Methanobrevibacter smithii from the sample of children feces, describe the physiological function of Methanobrevibacter smithii, annotate its functional gene, and to explore the in vitro utilization ability of carbohydrates difficult to digestible of the strain alone and in combination with the Bacteroides rhizobium which is important to the intestinal fermentation. We are also about to conducting diet-induced obesity C57BL/6 rice models, using 16S rDNA high-throughput sequencing to understand the distribution and abundance of Methanobrevibacter smithii in different parts of the digestive tract of normal mice and obese mice. Also, we intend to understand the effect of the transplantion of Methanobrevibacter smithii on obesity and focus on the the relationship between the Methanobrevibacter smithii and Bacteroides, and to see the impact of the transplantation of Methanobrevibacter smithii combined with the Bacteroides rhizobium on the development of immature mice obesity furtherly.

儿童肥胖问题日益恶化，迫切需要深入研究其发病机制和相关因素。肠道菌群与肥胖息息相关，其中产甲烷菌被认为在超重和肥胖发展方面存在作用，但还需要进一步研究。本研究基于课题组前期儿童队列研究发现的对儿童肥胖发展起重要作用的可能关键细菌，拟完成对儿童粪便标本中史氏产甲烷短杆菌的分离鉴定及生理功能描述、功能基因注释，并探索该菌单独及其与肠道重要发酵菌多形拟杆菌协同下对难消化碳水化合物的体外降解利用能力；同时通过C57BL/6小鼠及其饮食诱导肥胖动物模型研究，采用16SrDNA高通量测序了解史氏产甲烷短杆菌在正常小鼠和肥胖小鼠幼鼠消化道不同部位的分布与丰度差异，了解肥胖对史氏产甲烷短杆菌移植的影响，重点关注和分析产甲烷菌与肠道重要发酵菌如多形拟杆菌之间的相互联系，并进一步研究史氏产甲烷短杆菌单独移植、史氏产甲烷短杆菌与多形拟杆菌同时移植对C57BL/6小鼠幼鼠肥胖发生发展的影响。

儿童肥胖问题日益恶化，迫切需要深入研究其发病机制和相关因素。肠道菌群与肥胖息息相关,探讨肠道菌群、难消化碳水化合物与脂肪代谢的关联可为从益生元和肠道益生菌角度防治肥胖等代谢性疾病提供科学依据。项目基于小学学龄儿童研究队列基础，对比分析肥胖状态儿童与正常体重儿童肠道菌群多样性及菌群差异，发现学龄肥胖儿童肠道菌群多样性、优势益生菌属相对丰度较低，代谢紊乱相关菌属相对丰度较高，特有菌属中，与促进炎症、降低胆固醇代谢速率有关的细菌占优。对多形拟杆菌、动物双歧杆菌、粪肠球菌等肠道菌群利用五种难消化碳水化合物体外发酵增殖及产短链脂肪酸的研究，发现肠道菌群能利用难消化碳水化合物进行发酵，产生短链脂肪酸或其他酸性物质，对机体脂肪代谢有潜在影响，可为进一步深入了解肠道菌群在脂肪代谢方面的生理功能提供了初步数据。难消化碳水化合物菊粉、抗性淀粉RS3及其复合物对小鼠血脂水平及肠道菌群的影响研究，通过饮食干预实验动物模型发现菊粉和抗性淀粉RS3可以改善血脂水平和肠道菌群结构，同时显示出高脂、低脂饮食差异，菊粉和抗性淀粉RS3可能通过改变肠道菌群结构从而发挥降血脂作用，促进脂肪代谢，可以为未来运用靶向调节肠道菌群手段治疗代谢性疾病提供一定的科学依据。

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