Deciphering microbial interactions in synthetic human gut microbiome communities

Abstract

The ecological forces that govern the assembly and stability of the human gut microbiota remain unresolved. We developed a generalizable model‐guided framework to predict higher‐dimensional consortia from time‐resolved measurements of lower‐order assemblages. This method was employed to decipher microbial interactions in a diverse human gut microbiome synthetic community. We show that pairwise interactions are major drivers of multi‐species community dynamics, as opposed to higher‐order interactions. The inferred ecological network exhibits a high proportion of negative and frequent positive interactions. Ecological drivers and responsive recipient species were discovered in the network. Our model demonstrated that a prevalent positive and negative interaction topology enables robust coexistence by implementing a negative feedback loop that balances disparities in monospecies fitness levels. We show that negative interactions could generate history‐dependent responses of initial species proportions that frequently do not originate from bistability. Measurements of extracellular metabolites illuminated the metabolic capabilities of monospecies and potential molecular basis of microbial interactions. In sum, these methods defined the ecological roles of major human‐associated intestinal species and illuminated design principles of microbial communities.

Contrasting Strategies: Human Eukaryotic Versus Bacterial Microbiome Research

“…Representative synthetic communities can be used to isolate hypothesized organizational and causal relationships (e.g. Venturelli et al 2018). Even if these interactions occur naturally in much more complex communities, such simplifications nonetheless allow the identification of relevant causal variables, and the direction of causality.…”

Efficient engineered probiotics using synthetic biology approaches: A review

“…When gut microbiota is disturbed, the opportunistic pathogens overgrow. This condition increases the chances of hospital‐acquired infection (nosocomial infection), immune‐dysregulation, or metabolic imbalances, which lead to several diseases . To overcome such situations, functional foods and nutraceuticals (FFNs) have gained attention throughout the world.…”

Emergence of stable coexistence in a complex microbial community through metabolic cooperation and spatio-temporal niche partitioning

“…In large communities, both interspecies and species-environment interactions often act simultaneously leading to fascinating but intricate dynamics. This complexity has been difficult to dissect experimentally as the current experimental communities consist of few species, are cultivated ex situ under different conditions, or require inoculation from synthetic assemblies or original sources (Embree et al, 2014;Ponomarova et al, 2017;Venturelli et al, 2018;Wolfe et al, 2014). How natural communities realize stable coexistence has thus far remained mainly a question for theory.…”