BACKGROUND Accumulating evidence indicates that high-fat diet (HFD)-induced metabolic disorders are associated with dysbiosis of the gut microbiota. However, the sex-specific characteristics of the gut microbiota and its association with a sexually dimorphic response to a HFD remain unclear. METHODS Male and female mice were randomly assigned to receive a chow diet (CD) or HFD for 12 weeks. A group of HFD mice were pretreated with antibiotic cocktails for 4 weeks. Body weight, insulin sensitivity and the levels of serum metabolic parameters (blood glucose and insulin) were evaluated. 16S rRNA gene sequencing was performed to analyze the composition of the gut microbiota. RESULTS HFD-induced body weight gain (BWG) was higher in male mice than in female mice. While insulin resistance was increased in the HFD group compared to CD group in male mice, there was no difference in insulin resistance among female mice. Antibiotic-pretreatment alleviated HFD-induced insulin resistance in male mice and elevated fasting blood glucose in female mice. The composition of the gut microbiota in male mice was remarkably different from that in female mice independent of diet. A higher abundance of the genera Parabacteroides, Lactobacillus, Bacteroides, and Bifidobacterium was observed in females than inmales. HFD feeding also influenced the structure of the gut microbiota, as it decreased the abundance of short-chain fatty acids-producing bacteria including Roseburia and Lachnospiraceae_NK4A136_group. Alterations in the gut microbiota in response to antibiotics followed by HFD were different between males and females, indicating sex-dependent sensitivity to antibiotics. CONCLUSIONS We identified that sex had a greater impact on the composition of gut microbiota than environmental factors (HFD and antibiotics). The enrichment of beneficial microbes in female mice may be associated with the resistance of female mice to HFD-induced metabolic disorders, which was weakened by antibiotic pretreatment.

中文翻译：

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肠道微生物组与高脂饮食诱导的小鼠代谢紊乱之间的性别特异性关联。

背景技术越来越多的证据表明，高脂饮食（HFD）诱导的代谢紊乱与肠道菌群的营养不良有关。然而，尚不清楚肠道菌群的性别特异性特征及其与对HFD的性二态反应的关联。方法雄性和雌性小鼠随机分配为接受日粮（CD）或HFD，持续12周。一组HFD小鼠用抗生素混合物预处理了4周。评估体重，胰岛素敏感性和血清代谢参数（血糖和胰岛素）水平。进行16S rRNA基因测序以分析肠道菌群的组成。结果雄性小鼠的HFD诱导的体重增加（BWG）高于雌性小鼠。与CD组相比，HFD组的胰岛素抵抗在雄性小鼠中增加了，在雌性小鼠中，胰岛素抵抗没有差异。抗生素预处理减轻了雄性小鼠的HFD诱导的胰岛素抵抗，并提高了雌性小鼠的空腹血糖。不依赖饮食，雄性小鼠肠道菌群的组成与雌性小鼠明显不同。在雌性中观察到副细菌，乳杆菌，拟杆菌和双歧杆菌属的丰度高于雄性。HFD进食还影响了肠道菌群的结构，因为它降低了短链脂肪酸产生细菌（包括玫瑰果和Lachnospiraceae_NK4A136_group）的丰度。男性和女性对肠道微生物菌群的反应分别是对抗生素和HFD的反应有所不同，这表明性别对抗生素的敏感性不同。结论我们发现，与环境因素（HFD和抗生素）相比，性别对肠道菌群组成的影响更大。雌性小鼠中有益微生物的富集可能与雌性小鼠对HFD诱导的代谢紊乱的抵抗力有关，而抗生素预处理会削弱这种抵抗力。