Microbiome Interaction Network Toplologies to Improve Probiotic Ingress, Colonization, and Persistence across Varied Resident Communities

There is an increasing interest in delivering microbial probiotics to support the health of plants and animals. However, a challenge remains in ensuring that the active members of the probiotic can engraft into the host community sufficiently to deliver their desired effect. While there are many factors that can effect whether an organism will survive in a given environment, one of the critical factors is competition with the endogenous community members already present. The sporadic and unexplained failure of foreign species to inhabit environments suggests a need to consider resident microbial communities and their interspecies interactions when designing synthetic microbial community probiotics.

We hypothesize that a probiotic community can be composited such that supportive interactions among its members greatly increase the chances of survival and growth of its active members regardless of variation in composition of the endogenous population. We present a modeling and design framework to test this hypothesis and identify candidate synthetic community interaction networks which may serve this purpose.

Our microbial network optimization framework yielded microbial interaction network motifs for synthetic probiotics which, in simulation, promote better engraftment of a target species into diverse resident communities. Identified probiotic interaction networks are enriched for exploitative interactions between probiotic species. We find motif sign topology is critically important, while interaction magnitudes and species growth rate have little effect when varied within biological bounds. These results offer interaction motif templates that can be used to design synthetic microbial communities which reliably engraft into existing environments and their resident communities.