The human gut harbors a large and complex community of beneficial microbes that remain stable over long periods. This stability is considered critical for good health but is poorly understood. Here we develop a body of ecological theory to help us understand microbiome stability. Although cooperating networks of microbes can be efficient, we find that they are often unstable. Counterintuitively, this finding indicates that hosts can benefit from microbial competition when this competition dampens cooperative networks and increases stability. More generally, stability is promoted by limiting positive feedbacks and weakening ecological interactions. We have analyzed host mechanisms for maintaining stability-including immune suppression, spatial structuring, and feeding of community members-and support our key predictions with recent data.

The human body carries vast communities of microbes that provide many benefits. Our microbiome is complex and challenging to understand, but evolutionary theory provides a universal framework with which to analyse its biology and health impacts. Here we argue that to understand a given microbiome feature, such as colonization resistance, host nutrition or immune development, we must consider how hosts and symbionts evolve. Symbionts commonly evolve to compete within the host ecosystem, while hosts evolve to keep the ecosystem on a leash. We suggest that the health benefits of the microbiome should be understood, and studied, as an interplay between microbial competition and host control.

Antibiotic treatment can deplete the commensal bacteria of a patient’s gut microbiota and, paradoxically, increase their risk of subsequent infections. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), antibiotic administration is essential for optimal clinical outcomes but significantly disrupts intestinal microbiota diversity, leading to loss of many beneficial microbes. Although gut microbiota diversity loss during allo-HSCT is associated with increased mortality, approaches to reestablish depleted commensal bacteria have yet to be developed. We have initiated a randomized, controlled clinical trial of autologous fecal microbiota transplantation (auto-FMT) versus no intervention and have analyzed the intestinal microbiota profiles of 25 allo-HSCT patients (14 who received auto-FMT treatment and 11 control patients who did not). Changes in gut microbiota diversity and composition revealed that the auto-FMT intervention boosted microbial diversity and reestablished the intestinal microbiota composition that the patient had before antibiotic treatment and allo-HSCT. These results demonstrate the potential for fecal sample banking and posttreatment remediation of a patient’s gut microbiota after microbiota-depleting antibiotic treatment during allo-HSCT.

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The mammalian gut harbors a vast community of microorganisms -termed the microbiotawhose 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. 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).Coyte and Rakoff-Nahoum

Nowadays, microbial communities are frequently monitored over long periods of time and the interactions between their members are explored in vitro. This development has opened the way to apply mathematical models to characterize community structure and dynamics, to predict responses to perturbations and to explore general dynamical properties such as stability, alternative stable states and periodicity. Here, we highlight the role of dynamical systems theory in the exploration of microbial communities, with a special emphasis on the generalized Lotka-Volterra (gLV) equations. In particular, we discuss applications, assumptions and limitations of the gLV model, mention modifications to address these limitations and review stochastic extensions. The development of dynamical models, together with the generation of time series data, can improve the design and control of microbial communities.

Humans and many other hosts establish a diverse community of beneficial microbes anew each generation. The order and identity of incoming symbionts is critical for health, but what determines the success of the assembly process remains poorly understood. Here we develop ecological theory to identify factors important for microbial community assembly. Our method maps out all feasible pathways for the assembly of a given microbiome—with analogies to the mutational maps underlying fitness landscapes in evolutionary biology. Building these “assembly maps” reveals a tradeoff at the heart of the assembly process. Ecological dependencies between members of the microbiota make assembly predictable—and can provide metabolic benefits to the host—but these dependencies may also create barriers to assembly. This effect occurs because interdependent species can fail to establish when each relies on the other to colonize first. We support our predictions with published data from the assembly of the preterm infant microbiota, where we find that ecological dependence is associated with a predictable order of arrival. Our models also suggest that hosts can overcome barriers to assembly via mechanisms that either promote the uptake of multiple symbiont species in one step or feed early colonizers. This predicted importance of host feeding is supported by published data on the impacts of breast milk in the assembly of the human microbiome. We conclude that both microbe–microbe and host–microbe interactions are important for the trajectory of microbiome assembly.

Microbes often live in dense communities called biofilms, where competition between strains and species is fundamental to both evolution and community function. Although biofilms are commonly found in soil-like porous environments, the study of microbial interactions has largely focused on biofilms growing on flat, planar surfaces. Here, we use microfluidic experiments, mechanistic models, and game theory to study how porous media hydrodynamics can mediate competition between bacterial genotypes. Our experiments reveal a fundamental challenge faced by microbial strains that live in porous environments: cells that rapidly form biofilms tend to block their access to fluid flow and redirect resources to competitors. To understand how these dynamics influence the evolution of bacterial growth rates, we couple a model of flow-biofilm interaction with a game theory analysis. This investigation revealed that hydrodynamic interactions between competing genotypes give rise to an evolutionarily stable growth rate that stands in stark contrast with that observed in typical laboratory experiments: cells within a biofilm can outcompete other genotypes by growing more slowly. Our work reveals that hydrodynamics can profoundly affect how bacteria compete and evolve in porous environments, the habitat where most bacteria live. bacterial evolution | porous media flow | clogging | game theory | adaptive dynamics M odern microbiology relies on growing cells in liquid cultures and agar plates. Although these conditions offer high throughput and repeatability, they lack the complex physical and chemical landscapes that microbes experience in their natural environments. This environmental heterogeneity is increasingly recognized to exert a powerful influence on microbial ecology across a wide diversity of habitats, ranging from the ocean to the human gut (1-4). Although advances in sequencing technology now allow us to resolve how the genetic composition of microbial communities changes in response to environmental conditions (5, 6), we often lack a mechanistic understanding of the underlying processes. Novel empirical approaches, which simulate the conditions found in realistic microbial habitats, are needed to understand the strategies that cells use to gain an advantage over their competitors (7).The overwhelming majority of bacteria live in porous environments between the particles that compose soil, aquifers, and sediments, and cumulatively comprise roughly half of the carbon within living organisms globally (8). Cells in porous environments typically reside in surface attached structures known as biofilms (9), in which diverse bacterial genotypes live under intense competition for limited resources (10, 11). Recent efforts have identified specialized mechanisms that cells use to gain advantage over competing genotypes in biofilms, ranging from the secretion of toxins to polymer production and metabolic regulation (12-18). Whereas genotypic competition is most frequently studied in biofilms growing on simple flat surfaces (19-21...