老年小鼠肠道短链脂肪酸含量和菌群特征关联性探究

The Correlation Between The Content of Intestinal Short Chain Fatty Acid and Microflora Characteristics in Aged Mice

随着社会经济的发展,我国人口老龄化日益严重,衰老这个永恒的问题又一次引起人们的关注。肠道菌群失衡是衰老发生发展的关键因素,而短链脂肪酸(short chain fatty acids,SCFAs)是介导菌群影响机体的主要方式之一。研究衰老、肠道菌群及SCFAs三者之间的关系,能够为临床通过干预肠道菌群影响SCFAs含量,进而延缓衰老的治疗策略提供依据。本研究收集雄性青年(4月龄)和老年(20月龄)C57/BL6J小鼠的粪便,建立8种(乙酸、丙酸、异丁酸、丁酸、异戊酸、戊酸、己酸和庚酸)SCFAs的GC/MS含量测定方法。在青年小鼠和老年小鼠粪便中检测到乙酸、丙酸、异丁酸、丁酸、异戊酸和戊酸6种SCFAs,其中,乙酸、丙酸和丁酸含量较高。相较于青年小鼠,老年小鼠粪便中的乙酸(P<0.05)、异丁酸、丁酸、异戊酸和戊酸含量均显著降低(P<0.001)。采用16S rRNA测序,分析肠道菌群组成结构和菌属相对丰度变化,发现Prevotella(P<0.001)、Gemmiger(P<0.05)等丰度增加,而Sutterella(P<0.001)、Coprococcus(P<0.01)、Ruminococcus(P<0.01)和Adlercreutzia(P<0.01)等丰度减少。利用冗余分析(redundancy analysis,RDA)分析SCFAs含量与菌群的关联性。结果表明,Coprococcus、Anaerorhabdus、Ruminococcus、Adlercreutzia和Sutterella等与SCFAs呈正相关,而Prevotella、Anaeroplasma、Roseburia、Clostridium和Gemmiger等与SCFAs含量呈负相关。本研究表明,老年小鼠与青年小鼠肠道中SCFAs含量及肠道菌群特征紧密联系。相关性分析表明,Coprococcus和Ruminococcus等可能为影响SCFAs及成为监测及延缓衰老进程的关键菌属。本研究结果为临床通过干预肠道菌群影响SCFAs含量进而延缓衰老的治疗策略提供实验依据。

With the development of social economy,China’s population aging is increasingly serious.Therefore,there is renewed interest in the eternal problem of aging.The imbalance of the gut microbiota is a pivotal factor in the occurrence and development of aging,and the short chain fatty acids(SCFAs)are one of the main ways that mediate the influence of the gut microbiota on host.To investigate the relationship among aging,gut microbiota and SCFAs,this study provided a basis for clinical intervention in the gut microbiota to affect the content of SCFAs,thereby delaying aging.The feces of young(4 months old)and aged(20 months old)C57/BL6 J male mice were collected,and a rapid and sensitive method was developed and applied for the extraction and determination of eight SCFAs(acetic acid,propionic acid,isobutyric acid,butyric acid,isovaleric acid,pentanoic acid,hexanoic acid and heptanoic acid).The results showed that only six SCFAs of acetic acid,propionic acid,isobutyric acid,butyric acid,isovaleric acid and pentanoic acid were detected,and the content of acetic acid,propionic acid and butyric acid was higher.Compared with young mice,the contents of acetic acid(^(*)P<0.05),isobutyric acid,butyric acid,isovaleric aci and pentanoic acid(^(***)P<0.001)in the feces of aged mice were significantly reduced.Sequencing of 16 S rRNA was used to analyze the composition and structure of gut microbiota and the relative abundance of bacteria.The results found that the abundance of Prevotella(^(***)P<0.001)and Gemmiger(^(*)P<0.05)was increased,while the abundance of Sutterella(^(***)P<0.001),Coprococcus(^(**)P<0.01),Ruminococcus(^(**)P<0.01)and Adlercreutzia(^(**)P<0.01)was decreased.Redundancy analysis(RDA)was used to analyze the correlation between SCFAs content and gut microbiota,and the results showed that Coprococcus,Anaerorhabdus,Ruminococcus,Adlercreutzia and Sutterella were positively correlated with SCFAs,while Prevotella,Anaeroplasma,Roseburia,Clostridium and Gemmiger were negatively correlated with SCFAs.The content of SCFAs and the characteristics of gut microbiota in the feces of aged and young mice were closely related.Correlation analysis showed that Coprococcus and Ruminococcus may be the crucial bacteria that affect the production of SCFAs and monitor and delay the aging process.The research provided experimental evidence for clinical delay of aging by modulating gut microbiota via regulation of the SCFAs content.