Stronger connectivity of the resident gut microbiome lends resistance to invading bacteria

Abstract

Bacterial infection in the gut is often due to successful invasion of the host microbiome by an introduced pathogen. Ecological theory indicates that resident community members and their interactions should be strong determinants of whether an invading taxon can persist in a community. In the context of the gut microbiome, this suggests colonization resistance against newly introduced bacteria should depend on the instantaneous bacterial community composition within the gut and interactions between these constituent members. Here we develop a mathematical model of how metabolite-dependent biotic interactions between resident bacteria mediate invasion, and find that stronger biotic connectivity from metabolite cross-feeding and competition increases colonization resistance. We then introduce a statistical method for identifying invasive taxa in the human gut, and show empirically that greater connectivity of the resident gut microbiome is related to increased resistance to invading bacteria. Finally, we examined patient outcomes after fecal microbiota transplant (FMT) for recurring Clostridium difficile infection. Patients with lower connectivity of the gut microbiome after treatment were more likely to relapse, experiencing a later infection. Thus, simulation models and data from human subjects support the hypothesis that stronger interactions between bacteria in the gut repel invaders. These results demonstrate how ecological invasion theory can be applied to the gut microbiome, which might inform targeted microbiome manipulations and interventions. More broadly, this study provides evidence that low connectivity in gut microbial communities is a hallmark of community instability and susceptibility to invasion.