2. Academic Validation
  3. β-hydroxybutyrate inhibits Plasmodium falciparum development and confers protection against malaria in mice

β-hydroxybutyrate inhibits Plasmodium falciparum development and confers protection against malaria in mice

  • Nat Metab. 2025 Jul;7(7):1330-1343. doi: 10.1038/s42255-025-01302-0.
Zhiming Wei # 1 2,  Ning Jiang # 1 2,  Yiwei Zhang # 1 2,  Qilong Li # 1 2,  Ziwei Su 1 2,  Yanxin Zhang 1 2,  Kunying Lv 1 2,  Yixin Yang 1 2,  Tong Liu 1 2,  Lu Sun 1 2,  Kexin Zheng 1 2,  Ang Li 1 2,  Anni Feng 1 2,  Xiaoyu Sang 1 2,  Ying Feng 1 2,  Ran Chen 1 2,  Qijun Chen 3 4
Affiliations

Affiliations

  • 1 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.
  • 2 Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang, China.
  • 3 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. qijunchen759@syau.edu.cn.
  • 4 Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang, China. qijunchen759@syau.edu.cn.
  • # Contributed equally.
PMID: 40410577 DOI: 10.1038/s42255-025-01302-0
Abstract

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.

Figures
Products