Original Article

Subject Category: Integrated genomics and post-genomics approaches in microbial ecology

The ISME Journal (2014) 8, 1247–1258; doi:10.1038/ismej.2013.229; published online 9 January 2014

Breath gas metabolites and bacterial metagenomes from cystic fibrosis airways indicate active pH neutral 2,3-butanedione fermentation

Katrine L Whiteson1, Simone Meinardi2, Yan Wei Lim1, Robert Schmieder1, Heather Maughan3, Robert Quinn1, Donald R Blake2, Douglas Conrad4 and Forest Rohwer1

  1. 1Department of Biology, San Diego State University, San Diego, CA, USA
  2. 2Department of Chemistry, University of California, Irvine, CA, USA
  3. 3Ronin Institute, Montclair, NJ, USA
  4. 4Department of Medicine, University of California, San Diego, La Jolla, CA, USA

Correspondence: KL Whiteson, Biology Department LS301, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182, USA. E-mail: katrinewhiteson@gmail.com

Received 5 September 2013; Revised 14 November 2013; Accepted 15 November 2013
Advance online publication 9 January 2014



The airways of cystic fibrosis (CF) patients are chronically colonized by patient-specific polymicrobial communities. The conditions and nutrients available in CF lungs affect the physiology and composition of the colonizing microbes. Recent work in bioreactors has shown that the fermentation product 2,3-butanediol mediates cross-feeding between some fermenting bacteria and Pseudomonas aeruginosa, and that this mechanism increases bacterial current production. To examine bacterial fermentation in the respiratory tract, breath gas metabolites were measured and several metagenomes were sequenced from CF and non-CF volunteers. 2,3-butanedione was produced in nearly all respiratory tracts. Elevated levels in one patient decreased during antibiotic treatment, and breath concentrations varied between CF patients at the same time point. Some patients had high enough levels of 2,3-butanedione to irreversibly damage lung tissue. Antibiotic therapy likely dictates the activities of 2,3-butanedione-producing microbes, which suggests a need for further study with larger sample size. Sputum microbiomes were dominated by P. aeruginosa, Streptococcus spp. and Rothia mucilaginosa, and revealed the potential for 2,3-butanedione biosynthesis. Genes encoding 2,3-butanedione biosynthesis were disproportionately abundant in Streptococcus spp, whereas genes for consumption of butanedione pathway products were encoded by P. aeruginosa and R. mucilaginosa. We propose a model where low oxygen conditions in CF lung lead to fermentation and a decrease in pH, triggering 2,3-butanedione fermentation to avoid lethal acidification. We hypothesize that this may also increase phenazine production by P. aeruginosa, increasing reactive oxygen species and providing additional electron acceptors to CF microbes.


breath gas; cystic fibrosis; metagenomics; polymicrobial infection; metabolomics; biomarker