基于16S rDNA与1H NMR技术探讨高脂血症兔肠道菌群和代谢物变化

观察高脂血症模型兔的代谢物与肠道微生物变化并分析其相互关系。

雄性新西兰兔16只，随机分为正常组和模型组，每组8只。正常组喂普通饲料，模型组高胆固醇饮食。12周后比较2组兔血脂水平。利用16S rDNA测序技术检测兔粪便肠道菌群变化，采用¹H NMR代谢组学分析结肠代谢物改变。

与正常组比较，模型组兔血清LDL-C、TG、TC水平显著升高（均P＜0.01）；模型组兔肠道菌群结构发生改变，厚壁菌门、Lachnospiraceae_NK4A136_group、un_f_Lachnospiraceae、Subdoligranulum等菌群丰度上升，Lachnospiraceae_NK4B4_ group、un_o_Gastranaerophilales等菌属丰度下降。2组差异代谢物通路分析主要涉及谷氨酰胺与谷氨酸代谢，丙氨酸、天冬氨酸和谷氨酸代谢，磷脂代谢。Lachnospiraceae_NK4A136_group、un_f_Lachnospiraceae、un_o_Gastranaerophilales等菌属与差异代谢物有较强相关性。

高脂血症的病理过程可能通过Lachnospiraceae_NK4A136_group、un_f_Lachnospiraceae、Lachnospiraceae_NK4B4_group、un_o_Gastranaerophilales等菌属参与胆碱类代谢，谷氨酰胺与丙氨酸代谢，导致血脂代谢异常。

Changes of intestinal flora and metabolites in hyperlipidemia rabbits based on 16S rDNA and 1H NMR technology

ObjectiveTo observe the changes of metabolites and intestinal flora in hyperlipidemia model rabbits and explore their relationship. MethodsSixteen male New Zealand rabbits were randomly divided into normal group and model group with 8 rabbits in each group. The normal group was fed ordinary diet, while the model group was fed high cholesterol diet. The serum lipid levels in the two groups were compared after 12 weeks. The changes of fecal intestinal flora and colonic metabolites were analyzed using 16S rDNA and 1H NMR technique respectively. ResultsCompared with normal group, the serum LDL-C, TG and TC significantly increased in model group (all P＜0.01). The structure of intestinal flora changed, the abundances of Firmicutes, Lachnospiraceae_NK4A136_group, un_f_Lachnospiraceae and Subdoligranulum increased, and those of Lachnospiraceae_NK4B4_group and un_o_Gastranaerophilales decreased in model group. Pathway analysis indicated that the alterations of differential metabolites mainly involved in glutamine and glutamate metabolism, alanine, aspartate and glutamate metabolism and phospholipid metabolism. The abundances of Lachnospiraceae_NK4A136_group, un_f_Lachnospiraceae and un_o_Gastranaerophilales were strongly correlated with differential metabolites. ConclusionThe pathological process of hyperlipidemia may participate in choline metabolism, glutamine and alanine metabolism through Lachnospiraceae_NK4A136_group, un_f_Lachnospiraceae, Lachnospiraceae_NK4B4_group and un_o_Gastranaerophilales, resulting in abnormal lipid metabolism.