Understanding Competition and Cooperation within the Mammalian Gut Microbiome

Abstract

The mammalian gut harbors a vast community of microorganisms - termed the microbiota - whose composition and dynamics are considered to be critical drivers of host health. These factors depend, in part, upon the manner in which microbes interact with one another. Microbes are known to engage in a myriad of different ways, ranging from unprovoked aggression to actively feeding each other. However, the relative extent to which these different interactions occur between microbes within the gut is unclear. In this minireview we assess our current knowledge of microbe-microbe interactions within the mammalian gut microbiota, and the array of methods used to uncover them. In particular, we highlight the discrepancies between different methodologies: some studies have revealed rich networks of cross-feeding interactions between microbes, whereas others suggest that microbes are more typically locked in conflict and actively cooperate only rarely. We argue that to reconcile these contradictions we must recognize that interactions between members of the microbiota can vary across condition, space, and time - and that only through embracing this dynamism will we be able to comprehensively understand the ecology of our gut communities.

Figure 1.. Types of interactions by fitness effect and mechanism.

Pairwise interactions between species are defined based on the effect each microbe has on the other’s fitness, and on the mechanism by which that effect is achieved. Interactions in which one microbe is negatively affected and the other is either unaffected (-/0) or harmed (−/−) are defined as ammensal or competitive, respectively. When these interactions are mediated by competition for a nutrient they are termed exploitation, and interference refers to when the interaction is direct (for example, type VI killing). Interactions can also be asymmetric, when one species gains a fitness benefit at the expense of another (+/−). Positive interactions within the gut are typically either defined as cross-feeding when microbes grow on by-products, such as fermentation products, amino acids or digested sugars produced by others, or cooperation when one microbe has evolved an adaptation specifically to increase the fitness of another. These interactions can either be reciprocal (+/+) or not, in which case they are termed commensalism (+/0).

Figure 2.. Bottom-up and top-down approaches to infer microbe–microbe interactions within the gut microbiome.

Approaches to inferring microbe–microbe interactions within the mammalian microbiome can largely be divided into those that build an understanding from bottom-up reductionism (left), and those that attempt to learn interactions from top-down community data (right). Experimental reductionism (top left) often involves directly growing species together or culturing microbes in one another’s supernatant in order to assess the effects they have on one another’s growth. Reductionist computational methods (bottom left) can parse a given microbe’s genome to identify mechanisms for specific interactions (for example, microbial weapons) or apply metabolic-flux modeling to predict how species may compete for nutrients or cross-feed one another. By contrast, top-down approaches include experimentally perturbing an existing microbiota community in a defined manner (for example, by introducing a new species) and determining how members of the resident microbial community respond (top right); or, tracking an individual’s microbiota composition over time or across different conditions, and then using statistical tools to infer likely interactions between microbial taxa (bottom right).