Feeding with a ketonic diet confers complete protection against malaria

Environmental factors restrict malarial parasite development, but the influence of host metabolic variations on the infectivity of blood-stage parasite is not fully understood. Here, we show that the administration of a ketogenic diet (KD) to mice conferred complete protection against Plasmodim berghei infection. The β-hydroxybutyrate (βOHB), a predominant ketone body, was elevated in P. berghei infected mice on a KD, and inhibited the proliferation of both P. berghei and P. falciparum. A KD and βOHB induced metabolic reprogramming in the parasites resulting in reduced cellular nicotinamide adenine dinucleotide (NAD), which led to the downregulation of genes controlling parasite development, erythrocyte invasion and pathogenicity. This study reveal that A KD-derived βOHB can ultimately cause the developmental arrest of Plasmodium parasites and benefits host resistance to malaria. The underlying mechanism of ketone bodies-mediated parasite inhibition on P. falciparum was explored via single-cell RNA sequencing (scRNA-seq) analysis. A single-cell transcriptome atlas of P. falciparum 3D7 before and after βOHB treatment was first constructed