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Published August 12, 2020 | Published + Supplemental Material
Journal Article Open

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


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.

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, https://data.caltech.edu/records/1382.

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Supplemental Material - aba0353_SM.pdf

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