Research ArticleMICROBIOLOGY

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

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Science Advances  12 Aug 2020:
Vol. 6, no. 33, eaba0353
DOI: 10.1126/sciadv.aba0353
  • Fig. 1 Simplified illustration of multistability and hysteresis.

    A frictionless seesaw is a multistable system with two states (left and right) determined by the position of the person. Conversely, a seesaw with static friction is a multistable system with hysteresis. Within the region of hysteresis, the state of the system is not determined by the external input (position of person) but rather by the system’s history. As the person walks through positions 1 and 2 past the midpoint to position 3, the seesaw remains stuck in the left state; the person has to walk much further, to position 4, to switch it to the right state. As the person walks back to the left, through positions 5 and 6 and past the midpoint to position 7, the seesaw remains stuck in the right state and it only switches back to the left state when the person reaches position 8. In the region of positions 2, 3, 6, and 7, the system exhibits multistability and hysteresis (MSH). Here, the state of the microbial community (Kp-only state or Kp-Bt state) is analogous to the state of the seesaw, and the balance of oxygen or glucose inputs are analogous to the positions of the person.

  • Fig. 2 A multistable model system consisting of Kp, a facultative anaerobe, and Bt, an anaerobe, that is relevant to the human gut microbiome.

    (A) Dynamic equations describing the model system can be solved with dFBA using each species’ genome-scale metabolic model. (B) In the Kp-only state, Bt does not grow and Kp uses external sugars and short-chain fatty acids. (C) In the Kp-Bt state, Bt can grow and break down complex polysaccharides into simple sugars and short-chain fatty acids, which Kp can use to maintain reduced oxygen levels favorable for Bt growth.

  • Fig. 3 Simulations illustrating MSH in the microbial community with respect to environmental perturbations.

    Cell concentrations as a factor of (A) glucose concentration variations in the input feed under constant input oxygen flow rate (1.7 ml/min) and (B) input oxygen flow variations under constant glucose concentrations (3 mM) in the input feed. Each point represents the steady-state concentration for the given species in the community after a 50-hour simulation. (C) Regions of stability as a function of glucose concentrations in the input feed and oxygen flow rates into the reactor. In regions of multistability (circles), the community can exist in either a Kp-only state or a Kp-Bt (aerobe-anaerobe) state under the same conditions. In regions of monostability (triangles), it is only possible for one state to exist for the given set of parameters; down-pointed triangles represent monostable regions where Kp-only state exists, and up-pointed triangles represent monostable regions where only the Kp-Bt state can exist.

  • Fig. 4 MSH of Kp and Bt community in a CSTR.

    (A) Total cell concentrations collected at the eight different steady-state sample points (S1 to S8) from the CSTR measured by qPCR. (B) Cell concentrations for each individual species in the community measured by qPCR. (C) pH and dissolved oxygen concentrations measured in the CSTR for each sample point. Error bars are SD of at least three replicates collected at steady state (separated by >1 residence time of 5 hours) from the CSTR for each of the eight steady-state glucose conditions. See fig. S1 for bioreactor workflow.

  • Fig. 5 Gene expression analysis of CSTR steady-state samples.

    (A) PCA of the community transcriptome; each point represents the combined transcriptome of Kp and Bt for each sample (S1 to S8). (B) PCA of the Kp transcriptome. (C) The most differentially regulated pathway between the Kp-only and the Kp-Bt states is the PTS. The gray box indicates the up-regulated gene; white boxes are down-regulated genes. (D) PTS genes down-regulated in the Kp-Bt state in Kp. Solid lines represent the Kp-only state, and dashed lines represent the Kp-Bt state. (E) Gene expression, in transcripts per million (TPM), of oligosaccharide uptake in Kp and dextran metabolism to oligosaccharides in Bt for each steady-state sample point. (F) Expression of genes involved in acetate and lactate utilization in Kp and acetate and lactate production in Bt for each CSTR sample. (G) Expression of the propanediol utilization pathway in Kp. (E to G) Unshaded regions are the Kp-only state; the gray shaded region is the Kp-Bt state. Error bars are SD of three replicates collected (separated by >1 residence time) from the CSTR for each of the eight steady-state glucose conditions.

Supplementary Materials

  • Supplementary Materials

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

    Tahmineh Khazaei, Rory L. Williams, Said R. Bogatyrev, John C. Doyle, Christopher S. Henry, Rustem F. Ismagilov

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