Host-pathogen interactions can be influenced by the host microbiota, as the microbiota can facilitate or prevent pathogen infections. In addition, members of the microbiota can become virulent. Such pathobionts can cause co-infections when a pathogen infection alters the host immune system and triggers dysbiosis. Here we performed a theoretical investigation of how pathobiont co-infections affect the evolution of pathogen virulence. We explored the possibility that the likelihood of pathobiont co-infection depends on the evolving virulence of the pathogen. We found that, in contrast to the expectation from classical theory, increased virulence is not always selected for. For an increasing likelihood of co-infection with increasing pathogen virulence, we found scenario-specific selection for either increased or decreased virulence. Evolutionary changes, however, in pathogen virulence do not always translate into similar changes in combined virulence of the pathogen and the pathobiont. Only in one of the scenarios where pathobiont co-infection is triggered above a specific virulence level we found a reduction in combined virulence. This was not the case when the probability of pathobiont co-infection linearly increased with pathogen virulence. Taken together, our study draws attention to the possibility that host-microbiota interactions can be both the driver and the target of pathogen evolution. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.
Keywords: dysbiosis; mathematical model; microbiota; pathobiont; pathogen; virulence evolution.