小鼠肠道微生物相互作用具有抗高血糖作用

Liying Guo, Libing Xu, Yanhong Nie, Lu Liu, Zongping Liu, Yunpeng Yang
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引用次数: 0

摘要

肠道菌群与宿主代谢之间的相关性已被广泛研究,但肠道微生物相互作用对宿主代谢影响的相关研究却很少。在细菌素靶向策略的辅助下,我们旨在通过调整高脂肪饮食喂养小鼠的肠道微生物组成来鉴定与葡萄糖和脂质代谢相关的肠道微生物。为了实现这一目标,我们构建了单核细胞增生李斯特菌衍生的细菌素Lmo2776分泌模块,并将其整合到大肠杆菌Nissle 1917的基因组中,得到了分泌Lmo2776的菌株EcN-2776。EcN-2776给药可降低高脂饮食小鼠的血糖,升高血清甘油三酯。16S rRNA基因扩增子测序表明,Lmo2776的肠道分泌调节了高脂饮食小鼠肠道微生物组成。具体来说,Lmo2776抑制了鼠脂乳酸杆菌的生长,从而减轻了其对鼠粪杆菌的抑制作用。进一步的分析表明,给药粪草降低了高脂饮食小鼠的空腹血糖,这可能是通过粪草对葡萄糖的肠道消耗来实现的。我们的研究鉴定了与葡萄糖代谢相关的肠道微生物,揭示了它们之间的相互作用,破译了肠道微生物相互作用对宿主葡萄糖代谢的影响,为从肠道微生物相互作用的角度治疗高血糖铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Murine gut microbial interactions exert anti-hyperglycemic effects
The correlations between gut microbiota and host metabolism had been studied extensively, whereas little relevant work had been done to investigate the impact of gut microbial interactions on host metabolism. Assisted with bacteriocin-targeting strategy, we aimed to identify the glucose and lipid metabolism-associated gut microbes by adjusting the gut microbial composition of high-fat diet-fed mice. To fulfill this goal, the Listeria monocytogenes-derived bacteriocin Lmo2776 secretion module was constructed and integrated into the genome of Escherichia coli Nissle 1917, yielding the Lmo2776-secreting strain EcN-2776. EcN-2776 administration decreased the blood glucose and increased the serum triglyceride of high-fat diet-fed mice. 16S rRNA gene amplicon sequencing indicated that intestinal secretion of Lmo2776 adjusted the gut microbial composition of high-fat diet-fed mice. Specifically, Lmo2776 restricted the growth of Ligilactobacillus murinus, thus alleviating its inhibitory impact towards Faecalibaculum rodentium. Further analyses indicated that Faecalibaculum rodentium administration decreased the fasting blood glucose of high-fat diet-fed mice, which might be achieved by the intestinal consumption of glucose by Faecalibaculum rodentium. Our study identified the glucose metabolism-associated gut microbes, uncovered their interactions, deciphered the impact of gut microbial interaction on host glucose metabolism, and paved the way for treating hyperglycemia from the perspective of gut microbial interactions.
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