Table_1_Diet Control More Intensively Disturbs Gut Microbiota Than Genetic Background in Wild Type and ob/ob Mice.DOCX

Changes in environmental and genetic factors are vital to development of obesity and its complications. Induction of obesity and type 2 diabetes by both leptin deficiency (ob/ob) and high fat diet (HFD) has been verified in animal models. In the present experiment, three types of diets (normal diet; ND, HFD and high sucrose diet; HSD) and two types of genetic mice (Wild type: WT and ob/ob) were used to explore the relationship among diet supplements, gut microbiota, host genetics and metabolic status. HFD increased the body, fat and liver weight of both ob/ob and WT mice, but HSD did not. HFD also resulted in dyslipidemia, as well as increased serum transaminases and fasting glucose in ob/ob mice but not in WT mice, while HSD did not. Moreover, HFD led to brain BDNF elevation in WT mice and reduction in ob/ob mice, whereas HSD did not. Both HFD and HSD had a greater influence on gut microbiota than host genotypes. In detail, both of HFD and HSD alteration elucidated the majority (≥63%) of the whole structural variation in gut microbiota, however, host genetic mutation accounted for the minority (≤11%). Overall, diets more intensively disturbed the structure of gut microbiota in excess of genetic change, particularly under leptin deficient conditions. Different responses of host genotypes may contribute to the development of metabolic disorder phenotypes linked with gut microbiota alterations.

环境与遗传因素的变化对于肥胖及其并发症的发展至关重要。通过动物模型验证了由瘦素缺乏（ob/ob）和高脂肪饮食（HFD）诱导的肥胖和2型糖尿病。在本实验中，采用了三种类型的饮食（普通饮食；ND，高脂肪饮食；HFD和含高蔗糖饮食；HSD）以及两种遗传小鼠（野生型：WT和ob/ob）来探究饮食补充剂、肠道菌群、宿主遗传和代谢状态之间的关系。HFD增加了ob/ob和WT小鼠的体重、脂肪和肝脏重量，但HSD并未如此。HFD还导致ob/ob小鼠出现血脂异常，以及血清转氨酶和空腹血糖升高，而WT小鼠则未出现这些症状，HSD也未引起。此外，HFD导致WT小鼠大脑BDNF升高，而ob/ob小鼠则降低，HSD则未产生影响。HFD和HSD对肠道菌群的影响大于宿主基因型。具体而言，HFD和HSD的改变阐释了肠道微生物群整体结构变异的大部分（≥63%），而宿主基因突变仅占少数（≤11%）。总体而言，在瘦素缺乏的条件下，饮食对肠道微生物群结构的干扰程度超过遗传变化，尤其是对宿主基因型不同的个体。宿主基因型的不同反应可能有助于与肠道菌群改变相关的代谢紊乱表型的发生。