Gut Bacteroides act in a microbial consortium to cause susceptibility to severe malaria

Malaria, caused by Plasmodium species, remains a significant cause of morbidity and mortality globally. Gut bacteria can influence the severity of malaria, but the contribution of specific bacteria to the risk of severe malaria is unknown. Here, multiomics approaches demonstrate specific species of Bacteroides are causally linked to the risk of severe malaria. Plasmodium yoelii hyperparasitemia-resistant mice gavaged with murine-isolated Bacteroides fragilis develop P. yoelii hyperparasitemia. Moreover, Bacteroides are significantly more abundant in Ugandan children with severe malarial anemia than with asymptomatic P. falciparum infection. Human isolates of Bacteroides caccae, Bacteroides uniformis, and Bacteroides ovatus but not Bacteroides thetaiotaomicron caused susceptibility to severe malaria in mice. However, the pathogenic potential of gut Bacteroides towards susceptibility to severe malaria is dependent on additional gut microbiota, indicating a consortium effect in severe malaria. Approaches that target gut Bacteroides may present an opportunity to prevent severe malaria and associated deaths.