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Fig 1.

Flow chart of SCFA metabolism by bacterial species.

Solid lines are links between metabholites and producers/consumers, dashed lines show transformation of metabolites.

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Table 1.

Set of external parameters describing model.

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Fig 2.

Flow chart of bacterial behavior algorithm.

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Fig 3.

Feedbacks’ mechanisms.

(A) Toxin-antitoxin system: bacterium produces toxins, which are harmful to itself and digestible to the other bacterial type. (B) Bacteria of one type control abundance of the other bacterial type. (A) and (B) situations have been also examined in inversed edge directions. (C) Gut produces toxins, which are harmful to one bacterial type and digestible to the other one (toxin’s type is the same as in A case). (D) Gut controls abundance of bacterial species by producing toxins against one bacterial type (1 or 2). (E) Gut produces digestible substrates for bacteria of type 2.

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Table 2.

Feedbacks classification.

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Fig 4.

System stability.

(A) Multiple simulations with different initial bacteria numbers (axis 1—number of bacterial type 1, axis 2—number of bacterial type 2, axis 3—frequency of position). Basic schema with toxin-antitoxin systems FB1. One steady state is observed. (B) Multiple simulations with different initial bacteria numbers (axis 1—number of bacterial type 1, axis 2—number of bacterial type 2, axis 3—frequency of position). Basic schema with toxin-antitoxin systems (FB1) and mechanism of "feeding" bacterial type 1 as feedbacks (FB7). Two steady states are observed. (C) Part of artificial gut with FB1 (segregation index by bacterial type 1 0.55). (D) Part of artificial gut with FB1 and FB7 (segregation index by bacterial type 1: in mucin layer nearby gut wall 0.89, in mucin layer nearby gut lumen 0.62; segregation index by bacterial type 2: in mucin layer nearby gut lumen 0.38; in gut lumen 0.96). (E) Part of artificial gut with FB1 and FB7 (segregation index by bacterial type 1 in mucin layer nearby gut wall 0.82, in mucin layer nearby gut lumen 0.54; segregation index by bacterial type 2: in mucin layer nearby gut lumen 0.46; in gut lumen 0.96)

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Fig 5.

Dynamics of the system during antibiotic treatment.

(A) Change of bacterial quantity over time during antibiotic treatment. Bacteria are mixed. 2 feed backs. (periods of antibiotic gavage are highlighted on a graph). (B) Distribution of density of each bacterial type throughout the artificial gut width (axis y: density of bacterial type, axis x: 0mkm–bottom gut wall; 30000mkm–center of the gut). Bacteria are mixed. (C) Change of bacterial quantity over time during antibiotic treatment. Bacteria are separated into bacterial layers. (D) Distribution of density of each bacterial type throughout the artificial gut width (axis y: density of bacterial type, axis x: 0mkm–bottom gut wall; 30000mkm–center of the gut). Bacteria are separated into bacterial layers.

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Fig 6.

Dependence of the system resistance on number of feedbacks.

(A) Recovery time of "a steady state" dependence on duration of an antibiotic treatment course (once a day). (B) Resilience of the system with different numbers of feedbacks. Resilience is measured as time it takes system to reach critical threshold of 100 for any of bacterial types in case of continuous antibiotic treatment.

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Fig 7.

Classification of the community structure after treatment.

Changes of proportion of resistant bacteria (R/(R+S)) over time: (A) resistant strains dominate after treatment; (B) sensitive strains dominate after treatment (periods of antibiotic gavage are highlighted on a graph); (C) constant fluctuations in the ratio of resistant and sensitive strains. (D) Histogram of outcome distributions between 3 classes in percentage. (E) Classification results for the relevant parameters. Class 1 (red)—resistant strains dominate. Class 2 (green)—fluctuations in the ratio of resistant and sensitive strains. Class 3 (blue)—sensitive strains dominate.

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Fig 8.

Bacterial density along and across the artificial gut.

(A) Coexistence of sensitive and resistant strains after treatment (density along the gut length). (B) Coexistence of sensitive and resistant strains during antibiotic treatment. (C) Coexistence of sensitive and resistant strains during antibiotic treatment. Density distribution across gut (0 mkm–gut wall; 30000 mkm–center of the gut lumen).

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Fig 9.

Comparison of the graph properties between the microbiomes of the major studies.

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