Aggression is one of the most important social behaviors in nature for procreation and survival. However, understanding the underlying pathways and networks leading to aggression remains a major challenge. Although there has been some progress deciphering genetic factors and neural mechanisms influencing aggression, the precise networks and environmental factors controlling aggression remain a mystery. In this proposal, we suggest the novel concept that host aggression may be regulated in part by the microbiota. We and others have recently linked the gut microbiota, the overall constellation of microorganisms residing within our gut, to behaviors such as risk taking, mating and sexual behavior, as well as hormone production, regulation, and secretion. Here, we aim to characterize the effects of antibiotics, germ-free animal models, and specific microbes on aggression in flies and mice. We further hypothesize that these processes are mediated by pheromones, bacterial and host gene products, and host brain hormones, and will therefore test the involvement of these factors. Considering the microbiota as a novel element regulating aggression is an audacious concept. However, we have demonstrated in a preliminary study that elimination of the gut microbiota significantly raises aggression levels in both D. melanogaster and in mice, thereby providing strong initial support for our hypothesis that the microbiota is involved in regulation of aggression. Outcomes of this research will lead to a better understanding of the effects of microbiota on behavior in model systems, and open new horizons in recognition of pathways linking microbiota, hormones and aggression