The present project (acronym Malecon) aims at improving, innovating and validating the metagenomic approaches in the context of vector-borne diseases, where host patient, arthropod vector and pathogen interact between them and with their microbial communities. This proposal focuses on malaria disease, via tri-partite analyses of the microbiota of the three partners: human, Plasmodium and mosquito. The overall drive and rationale of the proposal originates from the concept that a complete understanding of malaria transmission must take into account the microbial ecosystem interacting with all the three players. We have therefore planned to implement metagenomic approaches to investigate the microbial profile of clinical samples from mild and severe malaria patients, parasite infected field-collected mosquitoes and Plasmodium to determine differences and similarities in the bacterial communities of mosquitoes, humans and potentially also parasite. We will also analyze in field-collected mosquitoes a possible correlation between microbial communities, immunity genes and salivary glands miRNAs repertoires. The ambition of the proposal is to determine whether components of the bacterial communities associated with the three partners affect the intensity of malaria transmission and the clinical course of the disease in humans. This will be beneficial to the refinement of existing control measures (targeted on either humans or mosquitoes) and to the development of novel strategies based on the use of symbionts as drug target or as a tool for symbiotic control. Moreover, data analysis standardization, streamlining and automation of thousands of samples will have a positive impact on reducing the time to market of Malecon’s “products”.