A Caltech Library Service

Metabolic multistability and hysteresis in a model aerobe-anaerobe microbiome community

Khazaei, Tahmineh and Williams, Rory L. and Bogatyrev, Said R. and Doyle, John C. and Henry, Christopher S. and Ismagilov, Rustem F. (2020) Metabolic multistability and hysteresis in a model aerobe-anaerobe microbiome community. Science Advances, 6 (33). Art. No. eaba0353. ISSN 2375-2548. PMCID PMC7423363. doi:10.1126/sciadv.aba0353.

[img] PDF - Published Version
Creative Commons Attribution.

[img] PDF (Figs. S1 to S9; Tables S1 to S4; Contributions of non-corresponding authors) - Supplemental Material
Creative Commons Attribution.


Use this Persistent URL to link to this item:


Major changes in the microbiome are associated with health and disease. Some microbiome states persist despite seemingly unfavorable conditions, such as the proliferation of aerobe-anaerobe communities in oxygen-exposed environments in wound infections or small intestinal bacterial overgrowth. Mechanisms underlying transitions into and persistence of these states remain unclear. Using two microbial taxa relevant to the human microbiome, we combine genome-scale mathematical modeling, bioreactor experiments, transcriptomics, and dynamical systems theory to show that multistability and hysteresis (MSH) is a mechanism describing the shift from an aerobe-dominated state to a resilient, paradoxically persistent aerobe-anaerobe state. We examine the impact of changing oxygen and nutrient regimes and identify changes in metabolism and gene expression that lead to MSH and associated multi-stable states. In such systems, conceptual causation-correlation connections break and MSH must be used for analysis. Using MSH to analyze microbiome dynamics will improve our conceptual understanding of stability of microbiome states and transitions between states.

Item Type:Article
Related URLs:
URLURL TypeDescription ItemSupplementary Materials ItemData CentralArticle
Khazaei, Tahmineh0000-0002-4743-2383
Williams, Rory L.0000-0003-2605-5790
Bogatyrev, Said R.0000-0003-0486-9451
Doyle, John C.0000-0002-1828-2486
Henry, Christopher S.0000-0001-8058-9123
Ismagilov, Rustem F.0000-0002-3680-4399
Additional Information:© 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). Submitted 30 October 2019; Accepted 26 June 2020; Published 12 August 2020. We thank J. Nielsen (Chalmers University of Technology), R. Murray (Caltech), J. Leadbetter (Caltech), and E. Hsiao (UCLA) for helpful discussions. We thank R. Poceviciute (Caltech) for imaging samples, K. Winzey (Caltech) for performing dPCR analysis of samples, and N. Shelby for contributions to writing and editing this manuscript. This work was supported, in part, by Army Research Office (ARO) MURI contract no. W911NF-17-1-0402, NSF Emerging Frontiers in Research and Innovation (EFRI) grant 1137089A, NSERC fellowship PGSD3-438474-2013 (to T.K.), and the Center for Environmental Microbial Interactions (CEMI). This work was also supported by the Millard and Muriel Jacobs Genetics and Genomics Laboratory at Caltech, and we thank director I. Antoshechkin for assistance. Author contributions: T.K., S.R.B., J.C.D., C.S.H., and R.F.I. conceptualized the study. T.K. and C.S.H. contributed to the computational investigation. T.K., R.L.W., and R.F.I. contributed to the experimental investigation. T.K. wrote the manuscript, and all authors contributed to the final submission of the manuscript. See the Supplementary Materials for detailed contribution statements. The authors declare that they have no competing interests. Data and materials availability: All associated raw sequencing data have been deposited in the Sequence Read Archive (Bio-Project Accession Number PRJNA580293). All other data are publicly available at CaltechDATA,
Group:Millard and Muriel Jacobs Genetics and Genomics Laboratory, Caltech Center for Environmental Microbial Interactions (CEMI)
Funding AgencyGrant Number
Army Research Office (ARO)W911NF-17-1-0402
Natural Sciences and Engineering Research Council of Canada (NSERC)PGSD3-438474-2013
Caltech Center for Environmental Microbial Interactions (CEMI)UNSPECIFIED
Millard and Muriel Jacobs Genetics and Genomics LaboratoryUNSPECIFIED
Issue or Number:33
PubMed Central ID:PMC7423363
Record Number:CaltechAUTHORS:20200813-144241318
Persistent URL:
Official Citation:T. Khazaei, R. L. Williams, S. R. Bogatyrev, J. C. Doyle, C. S. Henry, R. F. Ismagilov, Metabolic multistability and hysteresis in a model aerobe-anaerobe microbiome community. Sci. Adv. 6, eaba0353 (2020); doi: 10.1126/sciadv.aba0353
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:104959
Deposited By: Tony Diaz
Deposited On:13 Aug 2020 21:55
Last Modified:28 Feb 2023 22:00

Repository Staff Only: item control page