Malaria and Gut Microbiota: Microbial Interactions in the Host

Abstract

Malaria is still considered an important public health problem among parasitic diseases all over the world and poses a significant risk for half of the world's population. In recent years, both the human and animal experimental models pointed out that Plasmodium species that cause malaria changes the composition of the human gut microbiota and particularly certain gut bacterial communities are associated with the risk and severity of malaria infection. These data take the host-microbiota relationship to the next level and enable the scientific world to focus on the interaction in the host-microbiota-pathogen triangle. Plasmodium-gut microbiota interaction has attracted attention in the severe malaria infection, whose immunopathogenesis mechanism is still unknown and can show severe clinical symptoms from person to person. Studies on Plasmodium-gut microbiota are limited in the literature. Although it is difficult to compare the data due to the differences in method and purpose in the studies, in the case of Plasmodium infection, a decrease abundances of Bacteroidetes and Verrucomicrobia phyla and an increase abundances of Firmicutes and Proteobacteria phyla were observed in the gut microbiota. It has been noticed that Plasmodium can cause changes in the gut microbiota of the host and can differentiate the host immune response, especially by changing the short-chain fatty acids producing gut bacteria. The human immune response targets different stages in the complex life cycle of Plasmodium. The major immune response elements in the preerythrocytic and erythrocytic stages of Plasmodium are CD8+ T cells and antibodies, respectively. Germinal center B cells in the spleen have critical roles for the longevity of specific antibodies required in Plasmodium infections. Gut bacteria can influence germinal center B cell response in mice via CD40 ligand. Genes causing differentiation of Th17 cells are also upregulated in the late immune response to Plasmodium, and differentiation of Th17 cells has been found to be associated with changes in Sutterella and Parabacteroides distasonis in the gut microbiota. Data are currently limited to reveal causesconsequences relationships but the correlation of host cytokine responses due to malaria pathogenesis with the gut microbiota profile draws attention to the relationship. Although the changes in the human gut microbiota is examined in this review, it should be kept in mind that the microbiota in the midgut microbiota of Anopheles can have a negative effect on the physiology of Plasmodium. It was thought that the contribution of these differentiations in the host gut microbiota to the immune response and the host-microbiota-pathogen interaction, especially in severe malaria infections whose immunopathogenesis mechanism is not clear, should be investigated with standardized and comprehensive clinical studies. In this review article, human or animal studies on the interaction of Plasmodium-gut microbiota have been discussed.