Sheng Lili, Jena Prasant Kumar, Hu Ying, Wan Yu-Jui Yvonne
Department of Pathology and Laboratory Medicine, Davis Health, University of California, Sacramento, CA, USA.
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Hepatobiliary Surg Nutr. 2021 Jan;10(1):31-48. doi: 10.21037/hbsn-20-671.
Metabolism is sex-different, and the direct link between gut microbiota and aging-associated metabolic changes needs to be established in both sexes.
Gene expression, metabolic and inflammatory signaling, gut microbiota profile, and metabolome were studied during aging and after fecal microbiota transplantation (FMT) in mice of both sexes.
Our data revealed young female mice and aged male mice were the most insulin sensitive and resistant group, respectively. In addition, aging reduced sex difference in insulin sensitivity. Such age- and sex-dependent metabolic phenotypes were accompanied by shifted gut microbiota profile and altered abundance of bacterial genes that produce butyrate, propionate, and bile acids. After receiving feces from the aged males (AFMT), the most insulin-resistant group, recipients of both sexes had increased hepatic inflammation and serum endotoxin. However, AFMT only increased insulin resistance in female mice and abolished sex difference in insulin sensitivity. Additionally, such changes were accompanied by narrowed sex difference in metabolome. Metabolomics data revealed that age-associated insulin resistance in males was accompanied by increased sugar alcohols and dicarboxylic acids as well as reduced aromatic and branched-chain amino acids. Further, receiving feces from the young females (YFMT), the most insulin-sensitive group, reduced body weight and fasting blood glucose in male recipients and improved insulin sensitivity in females, leading to enhanced sex differences in insulin sensitivity and metabolome.
Aging systemically affected inflammatory and metabolic signaling based on the sex. Gut microbiome is age and sex-specific, which affects inflammation and metabolism in a sex-dependent manner.
新陈代谢存在性别差异，肠道微生物群与衰老相关代谢变化之间的直接联系需要在两性中建立。
在衰老过程中和对两性小鼠进行粪便微生物群移植（FMT）后，研究基因表达、代谢和炎症信号、肠道微生物群谱和代谢组。
我们的数据显示，年轻雌性小鼠和老年雄性小鼠分别是胰岛素敏感性最高和最低的组。此外，衰老降低了胰岛素敏感性的性别差异。这种年龄和性别依赖性的代谢表型伴随着肠道微生物群谱的改变以及产生丁酸、丙酸和胆汁酸的细菌基因丰度的变化。在接受来自最胰岛素抵抗组老年雄性的粪便（AFMT）后，两性受体的肝脏炎症和血清内毒素均增加。然而，AFMT仅增加了雌性小鼠的胰岛素抵抗，并消除了胰岛素敏感性的性别差异。此外，这些变化伴随着代谢组性别差异的缩小。代谢组学数据显示，男性与年龄相关的胰岛素抵抗伴随着糖醇和二羧酸的增加以及芳香族和支链氨基酸的减少。此外，接受来自最胰岛素敏感组年轻雌性的粪便（YFMT），降低了雄性受体的体重和空腹血糖，并改善了雌性的胰岛素敏感性，导致胰岛素敏感性和代谢组的性别差异增强。
衰老基于性别系统性地影响炎症和代谢信号。肠道微生物群具有年龄和性别特异性，以性别依赖的方式影响炎症和代谢。
