Abstract
Recent insights into the human microbiome offer the hope of manipulating its composition to help fight infectious diseases1–7. While this strategy has shown huge potential, its consequences for pathogen evolution have not been explored. Here we show that manipulating the microbiome to increase the competition that pathogens face could lead to the evolution of increased production of virulence factors that pathogens use to combat commensals, an evolutionary response that can increase total disease induced mortality in the long-term. However, if treatment with microbiome engineering is sufficiently aggressive this evolutionary response can be avoided and the pathogen eradicated. Furthermore, we show that using damage limitation therapies8 (e.g. antivirulence and anti-inflammatory drugs) in combination with microbiome manipulation increases the potential for pathogen eradication. While manipulating our microbiota offers a promising alternative to antibiotics, our results show that these treatments must be designed with careful consideration of the potential evolutionary responses of target pathogens.
