Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells
Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells
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DOI：
10.1016/j.cell.2020.04.027
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发表时间：
2020-06-11
期刊：
影响因子：
64.5
通讯作者：
Turnbaugh, Peter J.
中科院分区：
文献类型：
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作者：
Ang, Qi Yan;Alexander, Margaret;Turnbaugh, Peter J.
极低碳水化合物、高脂肪生酮饮食（KD）诱导代谢燃料利用的显著变化，从而提高循环酮体;然而，这些化合物对宿主-微生物组相互作用的影响仍不清楚。在这里，我们表明，KD以不同于高脂饮食（HFDs）的方式改变了人和小鼠的肠道菌群。一项为期8周的住院患者粪便样本的宏基因组学和代谢组学分析显示，KD期间肠道微生物群落结构和功能发生了显著变化。在小鼠中的梯度饮食实验证实了KD相对于HFD的独特影响，具有可再现的双歧杆菌耗竭。体外和体内实验表明，酮体选择性抑制双歧杆菌的生长。最后，将人类微生物组移植到无菌小鼠体内的单克隆和单克隆试验表明，KD相关肠道菌群降低了肠道促炎Th 17细胞的水平。总之，这些结果强调了跨领域化学对话对于介导宿主对饮食干预反应的重要性。
Very low-carbohydrate, high-fat ketogenic diets (KDs) induce a pronounced shift in metabolic fuel utilization that elevates circulating ketone bodies; however, the consequences of these compounds for host-microbiome interactions remain unknown. Here, we show that KDs alter the human and mouse gut microbiota in a manner distinct from high-fat diets (HFDs). Metagenomic and metabolomic analyses of stool samples from an 8-week inpatient study revealedmarked shifts in gutmicrobial community structure and function during the KD. Gradient diet experiments in mice confirmed the unique impact of KDs relative to HFDs with a reproducible depletion of bifidobacteria. In vitro and in vivo experiments showed that ketone bodies selectively inhibited bifidobacterial growth. Finally, mono-colonizations and human microbiome transplantations into germ-free mice revealed that the KD-associated gut microbiota reduces the levels of intestinal pro-inflammatory Th17 cells. Together, these results highlight the importance of trans-kingdom chemical dialogs for mediating the host response to dietary interventions.