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

Elife. 2018 Oct 16:7:e37090. doi: 10.7554/eLife.37090.

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.

Keywords: Blautia hydrogenotrophica; Faecalibacterium prausnitzii; Roseburia intestinalis; computational biology; infectious disease; microbiology; systems biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria / metabolism
  • Cells, Cultured
  • Computer Simulation
  • Fermentation
  • Formates / metabolism
  • Fructose / metabolism
  • Gastrointestinal Microbiome / genetics*
  • Gene Expression Regulation, Bacterial
  • Humans
  • Kinetics
  • Metabolome / genetics
  • Models, Biological
  • Prokaryotic Cells / metabolism
  • RNA, Ribosomal, 16S / genetics
  • Species Specificity
  • Transcriptome / genetics*

Substances

  • Formates
  • RNA, Ribosomal, 16S
  • formic acid
  • Fructose

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.