Integrated culturing, modeling and transcriptomics uncovers complex interactions and emergent behavior in a synthetic gut community

Abstract

Whereas the composition of the human gut microbiome is relatively well resolved, predictive understanding of its response to perturbations such as diet shifts is still lacking. Here, we followed a bottom-up strategy to explore human gut community dynamics. We established a synthetic community composed of three representative human gut isolates in well-controlled conditions in vitro. We then explored species interactions by performing all mono-and pair-wise fermentation experiments and quantified with a mechanistic community model how well tri-culture dynamics was predicted from mono-culture data. With the model as a reference, we demonstrated that species grown in co-culture behaved differently than in mono-culture and confirmed their altered behavior at the transcriptional level. In addition, we showed with replicate tri-cultures and in simulations that dominance in tri-culture sensitively depends on initial conditions. Our work has important implications for gut microbial community modeling as well as ecological interaction detection from batch cultures.

Ecophysiological insights into the human intestinal microbiota: from single strains to defined consortia

“…Reducing the complexity of natural microbiomes by growing few representative species in defined mixtures has been recently employed for investigating metabolic interactions and other ecological properties such as assembly in the intestinal microbiomes (D'hoe, et al 2018, Venturelli, et al 2018. However, most of the research was focused on defined co-cultures of two or three species, testing the occurrence of metabolic cross-feeding or competition (Belenguer, et al 2006, Sonnenburg, et al 2010, Chia, et al 2018, D'hoe, et al 2018. interactions.…”