肠道菌群在沙棘果多酚提取物调节机体脂代谢中的作用及机制研究

Cardiovascular diseases can be effectively prevented by the control of dyslipidemia. Polyphenol extracts from sea buckthorn (Hippophae rhamnoides L.) berry has anti-hyperlipidemia effect, which is attributed to its anti-oxidative, free radical scavenging, and anti-inflammatory abilities documented by previous studies. Recent evidence revealed that the disorder of host lipid metabolism has been closely related to gut microbiota. It has been confirmed that polyphenols are transformed into their metabolites by gut microbiota, resulting in the increasing bioavailability of polyphenols, and modulate the composition of the gut microbial community mostly through inhibiting pathogenic bacteria whilst promoting the proliferation of beneficial bacteria. In this study, we hypothesize that the ability to improve gut microbiota maybe another important mechanism for the anti-hyperlipidemia effect of polyphenol extracts from sea buckthorn berry. In this study, male Wistar rats will be fed with high-fat diet to establish hyperlipidemia model. After successfully modeling, they will be orally administrated with polyphenol extracts from sea buckthorn berry. Then we will collect stool samples, blood samples, intestinal tissue, and so on, and will detect blood lipid, antioxidant, blood glucose, inflammatory factor, and 16S rRNA gene of gut microbiota, to evaluate the effect of polyphenol extracts from sea buckthorn berry on the improvement of gut microbiota disorder induced by the high-fat diet. We will further employ antibiotic intervention experiment to ensure whether polyphenol extracts from sea buckthorn berry has the anti-hyperlipidemia effect without gut microbiota. Meanwhile, we will implement the fecal bacteria transplantation experiment to ensure whether the gut microbiota induced by polyphenol extracts from sea buckthorn berry will lead to the improvement of lipid metabolism. Furthermore, the levels of several bacterial metabolites will be evaluated, including lipopolysaccharide (LPS), Trimethylamine N-oxide (TMAO) in rat serum, and short chain fatty acids (SCFAs) in serum and stool, and intestinal mucosal barrier and permeability will also be evaluated to reveal the mechanisms of anti-hyperlipidemia property of polyphenol extracts from sea buckthorn berry via gut microbiota. Our study should provide a novel theoretical basic for the exploration of the health benefit from sea buckthorn and its mechanism of anti-hyperlipidemia effect.

控制血脂异常能有效预防心血管病，沙棘果多酚可降血脂，既往认为与抗氧化、抗炎有关。近来研究表明机体脂代谢与肠道菌群密切相关，且多酚需经肠道菌群代谢提高其生物利用度，同时能抑制致病菌促进有益菌生长。本研究探讨肠道菌群改善是否是沙棘果多酚降脂的重要机制之一。拟采用雄性Wistar大鼠，高脂饲料喂养，构建高脂血症模型，造模成功后给予沙棘果多酚提取物灌胃。收集粪样、血样和肠道组织，检测血脂、抗氧化、血糖、炎症，及粪样中细菌16S rRNA基因，探究多酚提取物对脂代谢和肠道菌群的影响。采用抗生素干预实验，探讨肠道菌群清除后多酚提取物能否降脂。同时采用粪菌移植实验，确认多酚提取物干预的肠道菌群能否引起脂代谢改变。进一步检测血清脂多糖、三甲胺氧化氮、短链脂肪酸含量，评价肠道粘膜屏障和通透性，探索多酚提取物经肠道菌群调节脂代谢的可能机制。本研究将为沙棘资源的有效利用及其影响脂代谢的机制提供新的理论依据。

控制血脂异常能有效预防心血管病，沙棘果多酚可降血脂，既往认为与抗氧化、抗炎有关。近来研究表明机体脂代谢与肠道菌群密切相关，且多酚需经肠道菌群代谢提高其生物利用度，同时能抑制致病菌促进有益菌生长。本研究探讨肠道菌群改善是否是沙棘果多酚降脂的重要机制之一。拟采用雄性Wistar大鼠，高脂饲料喂养，构建高脂血症模型，造模成功后给予沙棘果多酚提取物灌胃。收集粪样、血样和肠道组织，检测血脂、抗氧化、血糖、炎症，及粪样中细菌16S rRNA基因，探究多酚提取物对脂代谢和肠道菌群的影响。采用抗生素干预实验，探讨肠道菌群清除后多酚提取物能否降脂。同时采用粪菌移植实验，确认多酚提取物干预的肠道菌群能否引起脂代谢改变。进一步检测血清脂多糖、三甲胺氧化氮、短链脂肪酸含量，评价肠道粘膜屏障和通透性，探索多酚提取物经肠道菌群调节脂代谢的可能机制。本研究将为沙棘资源的有效利用及其影响脂代谢的机制提供新的理论依据。本研究分别评价了沙棘多酚对高脂饲料诱导的肥胖小鼠和db/db小鼠血脂代谢和肠道微生物的影响，发现沙棘干预后肥胖小鼠的总胆固醇、低密度脂蛋白胆固醇显著降低，db/db小鼠低密度脂蛋白显著降低而高密度脂蛋白显著升高。结合肝脏的病理结果发现，沙棘果干预后肥胖小鼠和db/db小鼠肝脏的脂肪堆积明显降低，脂肪变性减少。进一步对肠道菌群进行分析发现沙棘干预对肠道菌群影响显著，通过沙棘果多酚提取物干预，肠球菌属、乳杆菌属以及著名的减肥菌Akkermansia菌的丰度均显著增加，副拟杆菌属、norank_f__Oscillospiraceae、颤螺旋菌属(Oscillibacter)相对显著减少。综合可知，沙棘干预能有效改善小鼠脂代谢相关指标，其中肠道菌群中有益菌的增殖可能是其发挥作用的机制之一。