卫生研究

目的 阐述不同脂肪含量的饲料对定植了高甘油三酯人群肠道菌群大鼠脂代谢和肠道菌群构成情况的影响。方法 10周龄无菌SD大鼠，按体重随机分为3组，每组6只，对照组定植甘油三酯正常人群肠道菌群喂饲无菌鼠基础饲料，另两组定植高甘油三酯人群肠道菌群分别喂饲无菌鼠基础饲料和高脂饲料。以每100克体重1 mL的剂量给大鼠灌胃粪便菌液，隔天进行，共3次，之后进行2周菌群适应性生长，再用基础饲料或高脂饲料分别饲养相应组大鼠9周。检测大鼠体重变化、血脂水平、肝脏脂质沉积情况、肝功能与肠道菌群构成。结果 肠道菌群定植并持续不同饲料喂养9周后，基础饲料组大鼠的体重和脏器指数与对照组的差异无统计学意义，而高脂饲料组体重和脏器指数均显著高于基础饲料组(P<0.05或P<0.01)。基础饲料组血脂水平和肝功与对照组相比差异均无统计学意义，而高脂饲料组血清总胆固醇和低密度脂蛋白胆固醇水平分别为基础饲料组的1.4倍和1.8倍(P<0.01),丙氨酸氨基转移酶水平也显著高于基础饲料组(P<0.05)。基础饲料组肝脏脂滴面积比(18%)与对照组(17%)的差异无统计学意义，高脂饲料组肝脏脂滴面积比(41%)高于基础饲料组(P<0.01)。基础饲料组的肠道菌群α-多样性指数与对照组相近，而高脂饲料组Shannon指数低于基础饲料组(P<0.05)。在门水平和属水平上，高脂饲料组与基础饲料组肠道菌群构成差异明显，高脂饲料组厚壁菌门与拟杆菌门的相对丰度比值(3.37)高于基础饲料组(0.46)。血清脂质水平与肠道内特定菌群呈现显著关联关系。结论 膳食干预有助于改善血脂异常者的脂代谢水平，并有益于维持其正常的肠道菌群构成。

OBJECTIVE To elucidate the effects of diets differing in fat content on lipid metabolism and gut microbiota composition in rats colonized with the intestinal microbiota of hypertriglyceridemic humans.METHODS Ten-week-old germ-free SD rats were randomly assigned by body weight into three groups of six animals each. The control group was inoculated with gut microbiota from normotriglyceridemic humans and maintained on a standard sterile basal diet, whereas the other two groups received microbiota from hypertriglyceridemic humans and were fed either the same basal diet(NDG group)or a high-fat diet(HFDG group), respectively. A fecal microbial suspension was administered by gavage at 1 mL per 100 g body weight on alternate days for a total of three inoculations, followed by a 2-week period to allow microbiota engraftment and adaptation. Subsequently, the rats were maintained on their respective basal or high-fat diets for 9 weeks. Body-weight changes, serum lipid profiles, hepatic lipid accumulation, liver function indices, and gut microbiota composition were assessed.RESULTS After intestinal microbiota colonization followed by 9 weeks of continuous feeding on their respective diets, the NDG group exhibited higher body weight, liver index, epididymal fat index, and subcutaneous fat index than the control group, although none of these differences reached statistical significance. In contrast, the HFDG group was significantly elevated for all these parameters versus the control group, while its brown adipose tissue index was markedly lower. Serum lipid and hepatic function analyses revealed no significant differences between the control and NDG groups. Relative to the control group, the HFDG group displayed a 1.47-fold increase in serum total cholesterol(TC) and a 2.06-fold increase in LDL-C, both statistically significant. Serum ALT in the HFDG group was significantly higher than in controls(P<0.05), whereas AST showed an upward trend but lacked statistical significance. Histologically, the HFDG livers contained markedly more red-stained lipid droplets, and the droplet area fraction was significantly greater than in controls. Concurrently, microbial diversity in the HFDG group was lower than in the control group, and both phylum-and genus-level community structures diverged substantially from those of the NDG group. Furthermore, specific intestinal taxa were significantly correlated with circulating lipid levels, whereas no significant differences were observed between the control and NDG groups.CONCLUSION Dietary intervention can improve lipid metabolism and maintain normal gut microbiota composition in individuals with dyslipidemia.