BacArena: Individual-based metabolic modeling of heterogeneous microbes in complex communities

PLoS Comput Biol. 2017 May 22;13(5):e1005544. doi: 10.1371/journal.pcbi.1005544. eCollection 2017 May.

Abstract

Recent advances focusing on the metabolic interactions within and between cellular populations have emphasized the importance of microbial communities for human health. Constraint-based modeling, with flux balance analysis in particular, has been established as a key approach for studying microbial metabolism, whereas individual-based modeling has been commonly used to study complex dynamics between interacting organisms. In this study, we combine both techniques into the R package BacArena (https://cran.r-project.org/package=BacArena) to generate novel biological insights into Pseudomonas aeruginosa biofilm formation as well as a seven species model community of the human gut. For our P. aeruginosa model, we found that cross-feeding of fermentation products cause a spatial differentiation of emerging metabolic phenotypes in the biofilm over time. In the human gut model community, we found that spatial gradients of mucus glycans are important for niche formations which shape the overall community structure. Additionally, we could provide novel hypothesis concerning the metabolic interactions between the microbes. These results demonstrate the importance of spatial and temporal multi-scale modeling approaches such as BacArena.

MeSH terms

  • Biofilms
  • Gastrointestinal Microbiome / physiology
  • Humans
  • Metabolic Flux Analysis / methods*
  • Microbial Consortia / physiology*
  • Microbial Interactions / physiology*
  • Models, Biological*
  • Pseudomonas aeruginosa / metabolism

Grants and funding

This work was supported by the excellence cluster “Inflammation at Interfaces” (DFG support code EXC306), an ATTRACT program grant (FNR/A12/01), and an Aides a la Formation-Recherche (FNR/6783162) grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.