The dynamic landscape of parasitemia dependent intestinal microbiota shifting and the correlated gut transcriptome during Plasmodium yoelii infection.

Malaria, caused by Plasmodium, is a global life-threatening infectious disease. However, the dynamic interactions between intestinal microbiota and host immunity during the infections are still unclear. Here, we investigated the change of intestinal microbiome and transcriptome during Plasmodium yoelii infection in mice. The mice were infected with P. yoelii through the intraperitoneal injection. The intestinal contents and tissues were collected at different time points along with the malaria procession and they were subjected to the microbiome and transcriptome sequencing and analysis respectively. The dynamic landscape of parasitemia-dependent intestinal microbiota and related host immunity were identified: (1) The diversity and composition of the intestinal microbiota represented a significant correlation with the Plasmodium infection; (2) Up-regulated genes from the intestinal transcriptome were mainly enriched in immune cell differentiation pathways, especially, naive CD4+ T cell differentiation to Th1/2 cells in the early immune response and Th17 cells in the later immune stage, T cell receptor (TCR) and B cell receptor (BCR) activation in the whole host immunity; (3) Host immune cells presented parasitemia phase-specific characteristics against P. yoelii infection; (4) There were significant associations between the parasitemia phase-specific microbiotas and the host immune response. Th1 cell differentiation was positively correlated with genera Moryella and specie Erysipelotrichaceae bacterium canine oral taxon 255, while negatively correlated with genera Ruminiclostridium. Th17 cell differentiation was related to the colonization of family Peptococcaceae, genera Lachnospiraceae FCS020 group, and specie Eubacterium plexicaudatum ASF492 and the reduction of family Bacteroidales BS11 gut group, genera Sutterella, and specie Parabacteroides distasonis str. 3776 D15 I. BCRs and TCRs were highly related with the family Bacteroidales BS11 gut group, genera Moryella, and specie Erysipelotrichaceae bacterium canine oral taxon 255, but negatively related with the genera Ruminiclostridium. Our results indicated a remarkable dynamic landscape and correlation of the parasitemia-dependent shifting of intestinal microbiota and immunity, suggesting the essential roles of intestinal microbiome on the modulation of host immunity against Plasmodium infection.