Abstract

The composition of the human gut microbiome is well resolved, but predictive understanding of its dynamics 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 (Roseburia intestinalis L1-82, Faecalibacterium prausnitzii A2-165 and Blautia hydrogenotrophica S5a33) and explored their interactions under well-controlled conditions in vitro. Systematic mono- and pair-wise fermentation experiments confirmed competition for fructose and cross-feeding of formate. We quantified with a mechanistic model how well tri-culture dynamics was predicted from mono-culture data. With the model as reference, we demonstrated that strains grown in co-culture behaved differently than those in mono-culture and confirmed their altered behavior at the transcriptional level. In addition, we showed with replicate tri-cultures and simulations that dominance in tri-culture sensitively depends on the initial conditions. Our work has important implications for gut microbial community modeling as well as for ecological interaction detection from batch cultures.

Highlights

  • The human gut microbiome is a complex, spatially heterogeneous and dynamic ecosystem consisting of hundreds of species interacting with each other and with the human host

  • As we observed that F. prausnitzii A2-165 did not deplete fructose, presumably because of a lack of co-factors, we introduced a dependency on an undefined metabolite referred to as ‘unknown compound’

  • We found that B. hydrogenotrophica S5a33 is metabolically versatile and grew as fast as primary fermenters such as R. intestinalis L1-82

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Summary

Introduction

The human gut microbiome is a complex, spatially heterogeneous and dynamic ecosystem consisting of hundreds of species interacting with each other and with the human host. It is a daunting task to develop predictive models for such a system, yet the potential rewards are high and would, for instance, enable targeted interventions to shift dysbiotic communities towards more healthy states. Computational and Systems Biology Microbiology and Infectious Disease eLife digest Our gut is home to trillions of microorganisms, most of them bacteria, which have an important impact on our body. During healthy periods, these microorganisms help our digestion, protect our cells, and compete against disease-causing bacteria. Specific communities of gut bacteria are linked to many diseases

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