Wei Zhiming, Jiang Ning, Zhang Yiwei, Li Qilong, Su Ziwei, Zhang Yanxin, Lv Kunying, Yang Yixin, Liu Tong, Sun Lu, Zheng Kexin, Li Ang, Feng Anni, Sang Xiaoyu, Feng Ying, Chen Ran, Chen Qijun
Key Laboratory of Livestock Infectious Diseases, Ministry of Education, and Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China.
Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang, China.
Nat Metab. 2025 May 23. doi: 10.1038/s42255-025-01302-0.
Environmental factors restrict malaria parasite development, but the influence of host metabolic variations on the infectivity of the blood stage parasite is not fully understood. Here we show that mice on a ketogenic diet are completely protected from infection with the malaria parasite Plasmodium berghei. We further show that administration of the ketone body β-hydroxybutyrate (βOHB), but not of acetoacetate, increases survival of infected mice and inhibits proliferation of both P. berghei and Plasmodium falciparum in vitro. Administration of either a ketogenic diet or βOHB induces metabolic reprogramming in parasites, including reduced levels of nicotinamide adenine dinucleotide, which is associated with the downregulation of genes controlling parasite development, erythrocyte invasion and pathogenicity. Our data indicate that a ketogenic diet and the ketone body βOHB confer resistance to malaria in mice by causing developmental arrest of Plasmodium parasites, highlighting the potential of dietary and metabolic strategies to fight malarial infection.
环境因素限制疟原虫的发育，但宿主代谢变化对血液阶段疟原虫感染性的影响尚未完全了解。在此，我们表明，采用生酮饮食的小鼠对感染伯氏疟原虫具有完全的抵抗力。我们进一步表明，给予酮体β-羟基丁酸酯（βOHB），而非乙酰乙酸，可提高感染小鼠的存活率，并在体外抑制伯氏疟原虫和恶性疟原虫的增殖。采用生酮饮食或给予βOHB均可诱导疟原虫的代谢重编程，包括烟酰胺腺嘌呤二核苷酸水平降低，这与控制疟原虫发育、红细胞入侵和致病性的基因下调有关。我们的数据表明，生酮饮食和酮体βOHB通过导致疟原虫发育停滞，使小鼠对疟疾产生抗性，突出了饮食和代谢策略对抗疟疾感染的潜力。
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