Evolutionary modeling suggests that addictions may be driven by competition-induced microbiome dysbiosis

Abstract

Abstract Recent studies revealed mechanisms by which the microbiome affects its host’s brain, behavior and wellbeing, and that dysbiosis – persistent microbiome-imbalance – is associated with the onset and progress of various chronic diseases, including addictive behaviors. Yet, understanding of the ecological and evolutionary processes that shape the host-microbiome ecosystem and affect the host state, is still limited. Here we propose that competition dynamics within the microbiome, associated with host-microbiome mutual regulation, may promote dysbiosis and aggravate addictive behaviors. We construct a mathematical framework, modeling the dynamics of the host-microbiome ecosystem in response to alterations. We find that when this ecosystem is exposed to substantial perturbations, the microbiome may shift towards a composition that reinforces the new host state. Such a positive feedback loop augments post-perturbation imbalances, hindering attempts to return to the initial equilibrium, promoting relapse episodes and prolonging addictions. We show that the initial microbiome composition is a key factor: a diverse microbiome enhances the ecosystem’s resilience, whereas lower microbiome diversity is more prone to lead to dysbiosis, exacerbating addictions. This framework provides evolutionary and ecological perspectives on host-microbiome interactions and their implications for host behavior and health, while offering verifiable predictions with potential relevance to clinical treatments.