Dysbiosis Associated with Intestinal Pathology in Mice Infected with Malaria Parasites

Malaria caused by infection with protozoan parasites, genus Plasmodium, produces 200 million patients and 600 thousand deaths every year. In addition to malarial trias (fever, anemia, and splenomegaly) and fatal complications (cerebral malaria, renal failure), it is well known that gastrointestinal symptoms such as abdominal pain and diarrhea are frequently observed in malaria patients. However, the interactions between malaria pathology and intestinal microbiota have never been investigated. Here we investigated the intestinal pathology and microbiota in mice infected with a rodent malaria parasites P. berghei ANKA (PbA). We found that severe inflammatory changes occurred in the small intestines of C57BL/6 mice susceptible to experimental cerebral malaria (ECM) during PbA infection. Notably, we also found remarkable changes in composition of the intestinal microbiota, dysbiosis; decrease in symbiont bacteria and increase in pathobiont bacteria. The degree of intestinal pathology and dysbiosis was much milder in BALB/c mice resistant to ECM. Futhermore, the amount of some bacterial genera clearly correlated with disease severity of malaria, suggesting the relevance of intestinal microbiota to malaria pathogenicity. These results provide novel insights into host-parasite relationship in the intestines during malaria. We are now further investigating immune responses in gut-associated lymphoid tissues in these mice, and microbiota in patients with malaria.