Inferring Metabolic Mechanisms of Interaction within a Defined Gut Microbiota

Cell Syst. 2018 Sep 26;7(3):245-257.e7. doi: 10.1016/j.cels.2018.08.003. Epub 2018 Sep 5.


The diversity and number of species present within microbial communities create the potential for a multitude of interspecies metabolic interactions. Here, we develop, apply, and experimentally test a framework for inferring metabolic mechanisms associated with interspecies interactions. We perform pairwise growth and metabolome profiling of co-cultures of strains from a model mouse microbiota. We then apply our framework to dissect emergent metabolic behaviors that occur in co-culture. Based on one of the inferences from this framework, we identify and interrogate an amino acid cross-feeding interaction and validate that the proposed interaction leads to a growth benefit in vitro. Our results reveal the type and extent of emergent metabolic behavior in microbial communities composed of gut microbes. We focus on growth-modulating interactions, but the framework can be applied to interspecies interactions that modulate any phenotype of interest within microbial communities.

Keywords: emergent behavior; interspecies interactions; mathematical modeling; metabolic cross-feeding; metabolism; microbial community; microbial ecology; microbiome; microbiota; systems biology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Clostridium / physiology*
  • Coculture Techniques
  • Computer Simulation
  • Eubacterium / physiology*
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Lactobacillus / physiology*
  • Metabolic Networks and Pathways
  • Metabolome
  • Mice
  • Microbial Interactions*
  • Models, Biological
  • Models, Theoretical
  • Principal Component Analysis