A ketogenic diet can mitigate SARS-CoV-2 induced systemic reprogramming and inflammation

The ketogenic diet (KD) has demonstrated benefits in numerous clinical studies and animal models of disease in modulating the immune response and promoting a systemic antiinflammatory state. Here we investigate the effects of a KD on systemic toxicity in mice following SARS-CoV-2 infection. Our data indicate that under KD, SARS-CoV-2 reduces weight loss with overall improved animal survival. Muted multi-organ transcriptional reprogramming and metabolism rewiring suggest that a KD initiates and mitigates systemic changes induced by the virus. We observed reduced metalloproteases and increased inflammatory homeostatic protein transcription in the heart, with decreased serum pro-inflammatory cytokines (i.e., TNF-α, IL-15, IL-22, G-CSF, M-CSF, MCP-1), metabolic markers of inflammation (i.e., kynurenine/tryptophane ratio), and inflammatory prostaglandins, indicative of reduced systemic inflammation in animals infected under a KD. Taken together, these data suggest that a KD can alter the transcriptional and metabolic response in animals following SARS-CoV-2 infection with improved mice health, reduced inflammation, and restored amino acid, nucleotide, lipid, and energy currency metabolism. Bulk RNA sequencing comparing mouse tissues with differenet hACE2 genotype, Chow or Keto diet, and SARS-CoV-2 or Mock treatment

生酮饮食（ketogenic diet, KD）在多项疾病临床研究及动物模型中均展现出调节免疫应答、促进全身性抗炎状态的功效。本研究旨在探究生酮饮食对SARS-CoV-2感染小鼠全身性毒性的影响。数据显示，在生酮饮食干预条件下，SARS-CoV-2感染所致的体重丢失得以缓解，小鼠整体存活率显著提升。受抑制的多器官转录重编程与代谢重塑现象表明，生酮饮食可启动并缓解病毒诱导的全身性机体改变。我们观察到小鼠心脏组织中金属蛋白酶表达下调、炎症稳态蛋白转录上调；同时血清促炎细胞因子（即TNF-α、IL-15、IL-22、G-CSF、M-CSF、MCP-1）、炎症代谢标志物（即犬尿氨酸/色氨酸比值）及炎性前列腺素水平均有所降低，这表明生酮饮食干预下的感染小鼠全身性炎症反应得以减轻。综上，上述数据表明，生酮饮食可改变SARS-CoV-2感染后动物的转录与代谢应答，改善小鼠健康状况、减轻炎症，并恢复氨基酸、核苷酸、脂质及能量代谢稳态。本研究通过批量RNA测序（bulk RNA sequencing），对比了不同hACE2基因型、饲喂普通饲料（Chow）或生酮饮食（Keto），且经SARS-CoV-2感染或Mock处理的小鼠组织样本。