A cross-systems primer for synthetic microbial communities

Abstract

The design and use of synthetic communities, or SynComs, is one of the most promising strategies for disentangling the complex interactions within microbial communities, and between these communities and their hosts. Compared to natural communities, these simplified consortia provide the opportunity to study ecological interactions at tractable scales, as well as facilitating reproducibility and fostering interdisciplinary science. However, the effective implementation of the SynCom approach requires several important considerations regarding the development and application of these model systems. There are also emerging ethical considerations when both designing and deploying SynComs in clinical, agricultural or environmental settings. Here we outline current best practices in developing, implementing and evaluating SynComs across different systems, including a focus on important ethical considerations for SynCom research.

Figure 1.. Dual continuums of “question” and “system” for SynCom research.

Research questions using SynComs can range from fundamental questions or basic science, that is, trying to understand the rules and functioning underpinning different systems, to applied questions. Here communities are designed to fulfill certain purposes, for example, [AU: please complete this sentence using a brief example from the figure]. Likewise, the system being used can be placed on a continuum from environmental to free living and host-associated microbial communities.

Figure 2.. Flow diagram of approaches used when designing, evaluating and deploying a SynCom.

(A) All studies begin by designing the community (green). SynCom design can proceed from either Bottom-up (increase complexity through iterations) or Top-down (reduce complexity through iterations) approaches. When designing communities it is important to consider the number of strains needed to be relevant, as well as the sourcing of those strains. (B) Strains are then prepared and used for inoculation (yellow). Important considerations include the strain growth conditions, applied concentration, experimental system and methods of inoculation. (C) After a SynCom has been implemented, it is critical to evaluate if it provides relevant information about the system being modeled. To do so, the questions must first be well defined, after which the relevant features can be assessed by tracking the composition and functioning of the community. (D) When designing and applying SynComs across both human and environmental systems, there are important ethical considerations to take into account. In human systems, these communities should be representative of diversity seen across geographic, cultural and economic boundaries, and communities applied to patients should be tested for off target effects. When applying a SynCom to a natural system, care must be taken to ensure that these species do not spread and become invasive.

Figure 3.. Examples of bottom-up and top-down design approaches for SynComs.

(A) Bottom-up approaches can include selecting strains that represent the phylogenetic diversity of the natural community at some level, identifying strains that perform some functions of interest in the natural community, or through the prediction of key interactions in the community that a researcher might want to model. (B) Top-down designs can employ host or environmental filtering. This is where a larger community is applied into the study environment and only those strains that pass some growth or persistence metrics are included. It can also be achieved through the recapitulation of key features in community interaction networks or through a sequential drop out, where strains are sequentially removed in order to select the minimal complexity required to model the interactions of interest. In practice these approaches are not mutually exclusive, and researchers can choose to employ a combination of bottom-up or top-down strain selection approaches to define their communities.