Neurosciences, Furman University, Greenville, South Carolina, United States of America.
Department of Biology, Furman University, Greenville, South Carolina, United States of America.
PLoS One. 2022 Apr 6;17(4):e0265850. doi: 10.1371/journal.pone.0265850. eCollection 2022.
Rising obesity rates have become a major public health concern within the United States. Understanding the systemic and neural effects of obesity is crucial in designing preventive and therapeutic measures. In previous studies, administration of a high fat diet has induced significant weight gain for mouse models of obesity. Interestingly, sex differences in high-fat diet-induced weight gain have been observed, with female mice gaining significantly less weight compared to male mice on the same high-fat diet. It has also been observed that consumption of a high-fat diet can increase neurogliosis, but the mechanism by which this occurs is still not fully understood. Recent research has suggested that the gut microbiome may mediate diet-induced glial activation. The current study aimed to (1) analyze changes to the gut microbiome following consumption of a high fat (HF) diet as well as antibiotic treatment, (2) evaluate hippocampal microgliosis and astrogliosis, and (3) identify sex differences within these responses. We administered a low fat (Research Diets D12450 K) or high fat diet (Research Diets D12451) to male and female C57Bl/6 mice for sixteen weeks. Mice received an antibiotic cocktail containing 0.5g/L of vancomycin, 1.0 g/L ampicillin, 1.0 g/L neomycin, and 1.0 g/L metronidazole in their drinking water during the last six weeks of the study and were compared to control mice receiving normal drinking water throughout the study. We observed a significant reduction in gut microbiome diversity for groups that received the antibiotic cocktail, as determined by Illumina next-generation sequencing. Male mice fed the HF diet (± antibiotics) had significantly greater body weights compared to all other groups. And, female mice fed the low fat (LF) diet and administered antibiotics revealed significantly decreased microgliosis and astrogliosis in the hippocampus compared to LF-fed females without antibiotics. Interestingly, male mice fed the LF diet and administered antibiotics revealed significantly increased microgliosis, but decreased astrogliosis, compared to LF-fed males without antibiotics. The observed sex differences in LF-fed mice given antibiotics brings forward questions about sex differences in nutrient metabolism, gut microbiome composition, and response to antibiotics.
肥胖率的上升已成为美国主要的公共卫生关注点。了解肥胖的系统和神经效应对于设计预防和治疗措施至关重要。在之前的研究中，高脂肪饮食的管理已诱导肥胖的小鼠模型体重显著增加。有趣的是，已经观察到高脂肪饮食诱导的体重增加存在性别差异，与接受相同高脂肪饮食的雄性小鼠相比，雌性小鼠的体重增加明显较少。也已经观察到高脂肪饮食的摄入可以增加神经胶质增生，但发生这种情况的机制仍不完全清楚。最近的研究表明，肠道微生物组可能介导饮食诱导的神经胶质激活。本研究旨在：(1) 分析高脂肪（HF）饮食和抗生素治疗后肠道微生物组的变化；(2) 评估海马小胶质细胞和星形胶质细胞的增生；(3) 确定这些反应中的性别差异。我们给雄性和雌性 C57Bl/6 小鼠喂食低脂肪（Research Diets D12450 K）或高脂肪饮食（Research Diets D12451）十六周。在研究的最后六周，小鼠饮用水中添加含有 0.5g/L 万古霉素、1.0 g/L 氨苄青霉素、1.0 g/L 新霉素和 1.0 g/L 甲硝唑的抗生素混合物，并与整个研究期间接受普通饮用水的对照小鼠进行比较。我们通过 Illumina 下一代测序观察到接受抗生素混合物的组的肠道微生物组多样性显著降低。喂食高脂肪饮食（±抗生素）的雄性小鼠的体重明显大于其他所有组。并且，与未接受抗生素的 LF 喂养雌性小鼠相比，接受低脂肪（LF）饮食并给予抗生素的雌性小鼠的海马体中的小胶质细胞和星形胶质细胞增生明显减少。有趣的是，与未接受抗生素的 LF 喂养雄性小鼠相比，接受 LF 饮食并给予抗生素的雄性小鼠的小胶质细胞增生明显增加，但星形胶质细胞增生减少。接受抗生素的 LF 喂养雌性小鼠的观察到的性别差异提出了关于营养代谢、肠道微生物组组成和对抗生素的反应的性别差异的问题。
