Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
Buck Institute for Research on Aging, Novato, CA 94945, USA.
Cell. 2020 Jun 11;181(6):1263-1275.e16. doi: 10.1016/j.cell.2020.04.027. Epub 2020 May 20.
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 revealed marked shifts in gut microbial 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.
极低碳水化合物、高脂肪生酮饮食（KDs）可引起代谢燃料利用的显著变化，从而提高循环酮体水平；然而，这些化合物对宿主-微生物组相互作用的影响尚不清楚。在这里，我们表明 KDs 以一种与高脂肪饮食（HFDs）不同的方式改变了人类和小鼠的肠道微生物组。对 8 周住院研究的粪便样本进行的宏基因组和代谢组学分析显示，在 KD 期间肠道微生物群落结构和功能发生了明显变化。在小鼠中的梯度饮食实验证实了 KDs 相对于 HFDs 的独特影响，双歧杆菌可被重复性消耗。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，单定植和无菌小鼠中的人类微生物组移植显示，KD 相关的肠道微生物组降低了肠道促炎 Th17 细胞的水平。总之，这些结果强调了跨王国化学对话对于介导宿主对饮食干预的反应的重要性。
