Fig 1.
Design and characteristics of mmGEM.
A, Conceptual design of microbe-microbe interaction model (mmGEM) for simulating microbial association in MFC community. The mmGEM is a compartmentalized model consisting of microbial guild compartments (including sulfate-reducing bacteria (SRB), methanogens (MET), and sulfide-oxidizing bacteria (SOB)), and the community compartment (COM). The scheme also depicts the main substrate uptake (model inputs) and product generation (model outputs) of the studied community. B, Characteristics of the mmGEM model encompass the numbers of biochemical reactions, metabolites, and relevant metabolic genes. Venn diagram shows the number of exchange metabolites for each individual microbial guild and the number of common exchange metabolites that infers their cross-feeding association.
Fig 2.
Simulation of metabolic cross-feeding in L-OLR and H-OLR conditions.
A, Comparison of microbial relative abundances from experiments and microbe-microbe interaction model (mmGEM) simulations. B, The main metabolite exchange fluxes () between the key microbial guilds, including sulfate-reducing bacteria (SRB), methanogens (MET) and sulfide-oxidizing bacteria (SOB), and community compartment (COM) under low (L-OLR) and high organic loading conditions (H-OLR).
is an exchange reaction flux of the metabolite i in COM and the microbial group k, including SRB, MET, and SOB. Positive (+) and negative (-) exchange fluxes indicate metabolite secretion (+) and consumption (-) for microbial compartments, while representing metabolite influx (+) and efflux (-) for COM. Exchange fluxes on the x-axis are represented on an exponential scale.
Fig 3.
Differences in metabolic fluxes within the microbial community under H-OLR and L-OLR conditions.
The major metabolic cross-feedings () and intracellular flux (
) differences are represented as flux fold changes (FFCs; denoted as a number in rounded rectangles). The color of red and blue represent positive (+) and negative (-) FFCs, indicating increase and decrease of a reaction flux change in H-OLR, respectively. Intensity levels represent the degree of change, categorized as low (0.00<|FFC|<0.64), medium (0.64≤|FFC|<2), and high (|FFC|≥2) relative to the uptake rate of butyrate (0.64 FFC). Metabolites marked with yellow circles represent model input (data-specific conditions).
is exchange reaction flux of the metabolite i in community compartment (COM) and the microbial group k including sulfate-reducing bacteria (SRB), methanogen (MET), and sulfide-oxidizing bacteria (SOB).
is intracellular reaction fluxes of reaction j in the microbial group k including SRB, MET, and SOB. Abbreviations: SRB = sulfate-reducing bacteria, MET = methanogens, SOB = sulfide-oxidizing bacteria, COM = community compartment, Acoad1 = acyl-CoA dehydrogenase, Hacd1 = 3-hydroxyacyl-CoA dehydrogenase, ATPase = ATP synthase, Apr = adenylylsulfate reductase, Dsr = dissimilatory sulfite reductase, Pfor = pyruvate:ferredoxin oxidoreductase, Pepc = phosphoenolpyruvate carboxylase, Fpo = F420H2 dehydrogenase, Mtr = methyl transferase, and Hdr = heterodisulfide reductase.
Fig 4.
Simulated microbial growth rate and metabolic cross-feeding adaption under increasing organic concentration.
A, Microbial growth rates and B, exchange capacity fluxes () of sulfate-reducing bacteria (SRB), methanogens (MET), and sulfide-oxidizing bacteria (SOB) under increasing organic concentration. The fluxes of an exchange capacity across the increasing organic concentration range were normalized using min-max normalization. The first and second phases are separated by a dashed-blue line. The first phase is defined between 0.48 and 1.26 mmol
for butyrate uptake rate and 0.77 to 1.10 mmol
for acetate uptake rate. The second phase ranges from 1.37 to 3.61 and 1.15 to 2.09 mmol
for butyrate and acetate uptake rates, respectively. Dashed-grey lines represent points of the organic concentration, equal to low organic loading condition (L-OLR) and high organic loading conditions (H-OLR).
is exchange capacity flux of the metabolite i of microbial group k including SRB, MET, and SOB. Positive (+) and negative (-) normalized exchange capacity fluxes indicate metabolite secretion (+) and consumption (-) for microbial compartments.
Fig 5.
Manipulation of metabolic cross-feeding during increasing organic concentration.
A, Dominant microbial groups under varying sulfate-reducing bacteria (SRB) and sulfide-oxidizing bacteria (SOB) exchange capacities () and organic concentrations. Dots with black edges represent the original equilibrium of the exchange capacities of SRB-SOB under the low organic loading condition (L-OLR), and high organic loading conditions (H-OLR).
is an exchange capacity flux of the metabolite i of microbial group k including SRB, methanogen (MET), and SOB. B, Proposed microbial metabolic cross-feeding (
) at original and high SRB-SOB exchange capacities in H-OLR condition.
is exchange reaction flux of the metabolite i in community compartment (COM) and the microbial group k including SRB, MET, and SOB. Positive (+) and negative (-) exchange fluxes indicate metabolite secretion (+) and consumption (-) for microbial compartments, while representing metabolite influx (+) and efflux (-) for COM. The exchange fluxes on x-axis are represented in an exponential scale.
Fig 6.
Influence of SRB-SOB exchange capacity on microbial relative abundance.
Linear relationships between the exchange capacities () and relative abundances, of sulfide-oxidizing bacteria (SOB) and methanogens (MET).
is an exchange capacity flux of the metabolite i of microbial group k including sulfate-reducing bacteria (SRB), MET, and SOB.
Fig 7.
High H+ concentration supports growth and metabolic cross-feeding of SOB.
A, Relative abundances of microbes including sulfate-reducing bacteria (SRB), methanogens (MET), and sulfide-oxidizing bacteria (SOB), and B, Intercellular cross-feeding and intracellular fluxes of SOB during increasing H+ concentration (). The simulated fluxes were normalized by min-max normalization. Positive (+) and negative (-) normalized fluxes of exchanges indicate metabolite secretion (+) and consumption (-) in SOB.