Mining the Human Host Metabolome Toward an Improved Understanding of Malaria Transmission

The big data movement has led to major advances in our ability to assess vast and complex datasets related to the host and parasite during malaria infection. While host and parasite genomics and transcriptomics are often the focus of many computational efforts in malaria research, metabolomics represents another big data type that has great promise for aiding our understanding of complex host-parasite interactions that lead to the transmission of malaria. Recent analyses of the complement of metabolites present in human blood, skin and breath suggest that host metabolites play a critical role in the transmission cycle of malaria. Volatile compounds released through breath and skin serve as attractants to mosquitoes, with malaria-infected hosts appearing to have unique profiles that further increase host attractiveness. Inside the host, fluctuations in the levels of certain metabolites in blood may trigger increased production of transmission-competent sexual stages (gametocytes), setting the stage for enhanced transmission of malaria from human to mosquito. Together, these recent discoveries suggest that metabolites of human blood, skin and breath play critical roles in malaria transmission. This review discusses recent advances in this area, with a focus on metabolites that have been identified to play a role in malaria transmission and methods that may lead to an improved understanding of malaria transmission.