Abstract:
Gut dysbiosis is linked to metabolic and neurodegenerative diseases and comprises a plausible link between high-fat diet (HFD) and brain dysfunction. Here we show that gut microbiota modulation by either antibiotic treatment for 5 weeks or a brief 3-day fecal microbiota transplantation (FMT) regimen from low-fat (control) diet-fed mice decreased weight gain, adipose tissue hypertrophy, and glucose intolerance induced by HFD in C57BL/6 male mice. Notably, gut microbiota modulation by FMT completely reversed impaired recognition memory induced by HFD, whereas modulation by antibiotics had less pronounced effect. Improvement in recognition memory by FMT was accompanied by decreased HFD-induced astrogliosis in the hippocampal cornu ammonis region. Gut microbiome composition analysis indicated that HFD diminished microbiota diversity compared to control diet, whereas FMT partially restored the phyla diversity. Our findings reinforce the role of the gut microbiota on HFD-induced cognitive impairment and suggest that modulating the gut microbiota may be an effective strategy to prevent metabolic and cognitive dysfunction associated with unfavorable dietary patterns.
摘要:
肠道菌群失调与代谢和神经退行性疾病有关,并且在高脂肪饮食(HFD)和脑功能障碍之间存在合理的联系。在这里,我们表明通过抗生素治疗5周或从低脂(对照)饮食喂养的小鼠中进行短暂的3天粪便微生物群移植(FMT)方案来调节肠道微生物群,从而减少了体重增加,脂肪组织肥大,HFD诱导的C57BL/6雄性小鼠葡萄糖耐受不良。值得注意的是,FMT对肠道菌群的调节完全逆转了HFD诱导的识别记忆受损,而抗生素的调节效果不那么明显。FMT改善了识别记忆,同时减少了HFD诱导的海马区星形胶质细胞增生。肠道微生物组组成分析表明,与对照饮食相比,HFD减少了微生物群多样性,而FMT部分恢复了门的多样性。我们的发现加强了肠道微生物群在HFD诱导的认知障碍中的作用,并表明调节肠道微生物群可能是预防与不良饮食模式相关的代谢和认知功能障碍的有效策略。