RT Journal Article SR Electronic T1 Metabolic multistability and hysteresis in a model aerobe-anaerobe microbiome community JF Science Advances JO Sci Adv FD American Association for the Advancement of Science SP eaba0353 DO 10.1126/sciadv.aba0353 VO 6 IS 33 A1 Khazaei, Tahmineh A1 Williams, Rory L. A1 Bogatyrev, Said R. A1 Doyle, John C. A1 Henry, Christopher S. A1 Ismagilov, Rustem F. YR 2020 UL http://advances.sciencemag.org/content/6/33/eaba0353.abstract AB 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.