ABSTRACT
The human gut microbiota relies on complex carbohydrates (glycans) for energy and growth, primarily dietary fiber and host-derived mucins. We introduce a mathematical model of a glycan generalist and a mucin specialist in a two-compartment chemostat model of the human colon. Our objective is to characterize the influence of dietary fiber and mucin supply on the abundance of mucin-degrading species within the gut ecosystem. Current mathematical gut reactor models that include the enzymatic degradation of glycans do not differentiate between glycan types and their degraders. The model we present distinguishes between a generalist that can degrade both dietary fiber and mucin, and a specialist species that can only degrade mucin. The integrity of the colonic mucus barrier is essential for overall human health and well-being, with the mucin specialist Akkermanisa muciniphila being associated with a healthy mucus layer. Competition, particularly between the specialist and generalists like Bacteroides thetaiotaomicron, may lead to mucus layer erosion, especially during periods of dietary fiber deprivation. Our model treats the colon as a gut reactor system, dividing it into two compartments that represent the lumen and the mucus of the gut, resulting in a complex system of ordinary differential equations with a large and uncertain parameter space. To understand the influence of model parameters on long-term behavior, we employ a random forest classifier, a supervised machine learning method. Additionally, a variance-based sensitivity analysis is utilized to determine the sensitivity of steady-state values to changes in model parameter inputs. By constructing this model, we can investigate the underlying mechanisms that control gut microbiota composition and function, free from confounding factors.
Subject(s)
Dietary Fiber , Gastrointestinal Microbiome , Models, Biological , Mucins , Mucus , Mucins/metabolism , Dietary Fiber/metabolism , Humans , Gastrointestinal Microbiome/physiology , Mucus/metabolism , Colon/metabolism , Colon/microbiology , Polysaccharides/metabolismABSTRACT
The interactions between marine bacteria and particulate matter play a pivotal role in the biogeochemical cycles of carbon and associated inorganic elements in the oceans. Eutrophic plumes typically form around nutrient-releasing particles and host intense bacterial activities. However, the potential of bacteria to reshape the nutrient plumes remains largely unexplored. We present a high-resolution numerical analysis for the impacts of nutrient uptake by free-living bacteria on the pattern of dissolution around slow-moving particles. At the single-particle level, the nutrient field is parameterized by the Péclet and Damköhler numbers (0 < Pe < 1000, 0 < Da < 10) that quantify the relative contribution of advection, diffusion and uptake to nutrient transport. In spite of reducing the extent of the nutrient plume in the wake of the particle, bacterial uptake enhances the rates of particle dissolution and nutrient depletion. These effects are amplified when the uptake timescale is shorter than the plume lifetime (Pe/Da < 100, Da > 0.0001), while otherwise they are suppressed by advection or diffusion. Our analysis suggests that the quenching of eutrophic plumes is significant for individual phytoplankton cells, as well as marine aggregates with sizes ranging from 0.1 mm to 10 mm and sinking velocities up to 40 m per day. This microscale process has a large potential impact on microbial growth dynamics and nutrient cycling in marine ecosystems.
ABSTRACT
We propose a new mathematical framework for the addition of stochastic attachment to biofilm models, via the use of random ordinary differential equations. We focus our approach on a spatially explicit model of cellulolytic biofilm growth and formation that comprises a PDE-ODE coupled system to describe the biomass and carbon respectively. The model equations are discretized in space using a standard finite volume method. We introduce discrete attachment events into the discretized model via an impulse function with a standard stochastic process as input. We solve our model with an implicit ODE solver. We provide basic simulations to investigate the qualitative features of our model. We then perform a grid refinement study to investigate the spatial convergence of our model. We investigate model behaviour while varying key attachment parameters. Lastly, we use our attachment model to provide evidence for a stable travelling wave solution to the original PDE-ODE coupled system.
Subject(s)
Biofilms , Models, Theoretical , Biomass , Computer Simulation , Models, BiologicalABSTRACT
We formulate a multiscale mathematical model that describes the bioreduction of uranium in porous media. On the mesoscale we describe the bioreduction of uranium [VI] to uranium [IV] using a multispecies one-dimensional biofilm model with suspended bacteria and thermodynamic growth inhibition. We upscale the mesoscopic (colony scale) model to the macroscale (reactor scale) and investigate the behavior of substrate utilization and production, attachment and detachment processes, and thermodynamic effects not usually considered in biofilm growth models. Simulation results of the reactor model indicate that thermodynamic inhibition quantitatively alters the dynamics of the model and neglecting thermodynamic effects may over- or underestimate chemical concentrations in the system. Furthermore, we numerically investigate uncertainties related to the specific choice of attachment and detachment rate coefficients and find that while increasing the attachment rate coefficient or decreasing the detachment rate coefficient leads to thicker biofilms, performance of the reactor remains largely unaffected.
Subject(s)
Uranium , Biofilms , Bioreactors , Culture Media , Mathematical Concepts , PorosityABSTRACT
We formulate a biofilm reactor model with suspended bacteria that accounts for thermodynamic growth inhibition. The reactor model is a chemostat style model consisting of a single replenished growth promoting substrate, a single reaction product, suspended bacteria, and wall attached bacteria in the form of a bacterial biofilm. We present stability conditions for the washout equilibrium using standard techniques, demonstrating that analytical results are attainable even with the added complexity from thermodynamic inhibition. Furthermore, we numerically investigate the longterm behaviour. In the computational study, we investigate model behaviour for select parameters and two commonly used detachment functions. We investigate the effects of thermodynamic inhibition on the model and find that thermodynamic inhibition limits substrate utilization/production both inside the biofilm and inside the aqueous phase, resulting in less suspended bacteria and a thinner biofilm.
Subject(s)
Bacterial Physiological Phenomena , Biofilms , Models, Biological , Thermodynamics , Bacteria/growth & development , BioreactorsABSTRACT
Unusually high wintering losses of Apis mellifera in recent years has raised concerns regarding the well-being and productivity of honey bees across the globe. While these losses are likely multi-factorial, a proposed contributor are diseases, including those caused by parasites. We formulate and present a mathematical model for a colony of Apis mellifera honey bees infected with the microsporidian parasite Nosema ceranae. The model is numerically analyzed to determine the effects of N. ceranae infection on population and food storage dynamics and their subsequent implications towards colony survival and annual honey yield. Depending on the strength of disease, it is possible for either parasite fadeout, co-existence between bees and N. ceranae, or colony failure to occur. In all cases, the yield of honey collected by the beekeeper is reduced. We further extend the model to include various treatment schemes with the, now discontinued, antimicrobial fumagillin. Treatment with fumagillin can reduce the risk of colony failure and will increase honey yield compared to when no treatment is applied.
ABSTRACT
We formulate a mathematical model of bacterial populations in a chemostat setting that also accounts for thermodynamic growth inhibition as a consequence of chemical reactions. Using only elementary mathematical and chemical arguments, we carry this out for two systems: a simple toy model with a single species, a single substrate, and a single reaction product, and a more involved model that describes bioreduction of uranium[VI] into uranium[IV]. We find that in contrast to most traditional chemostat models, as a consequence of thermodynamic inhibition the equilibria concentrations of nutrient substrates might depend on their inflow concentration and not only on reaction parameters and the reactor's dilution rate. Simulation results of the uranium degradation model indicate that thermodynamic growth inhibition quantitatively alters the solution of the model. This suggests that neglecting thermodynamic inhibition effects in systems where they play a role might lead to wrong model predictions and under- or over-estimate the efficacy of the process under investigation.
Subject(s)
Bacteria/growth & development , Bacteria/metabolism , Models, Biological , Uranium/pharmacokinetics , Biodegradation, Environmental , Bioreactors , Computational Biology , Computer Simulation , Mathematical Concepts , Oxidation-Reduction , Thermodynamics , Uranium/chemistryABSTRACT
We propose a mathematical framework for introducing random attachment of bacterial cells in a deterministic continuum model of cellulosic biofilms. The underlying growth model is a highly nonlinear coupled PDE-ODE system. It is regularised and discretised in space. Attachment is described then via an auxiliary stochastic process that induces impulses in the biomass equation. The resulting system is an Itô stochastic differential equation. Unlike the more direct approach of modeling attachment by additive noise, the proposed model preserves non-negativity of solutions. Our numerical simulations are able to reproduce characteristic features of cellulolytic biofilms with cell attachment from the aqueous phase. Grid refinement studies show convergence for the expected values of spatially integrated biomass density and carbon concentration. We also examine the sensitivity of the model with respect to the parameters that control random attachment.
Subject(s)
Biofilms , Models, Biological , Biomass , Computer Simulation , Stochastic ProcessesABSTRACT
Traditionally, the evaluation of cardiac function has focused on systolic function; however, there is a growing appreciation for the contribution of diastolic function to overall cardiac health. Given the emerging interest in evaluating diastolic function in all models of heart failure, there is a need for sensitivity, accuracy, and precision in the hemodynamic assessment of diastolic function. Hemodynamics measure cardiac pressures in vivo, offering a direct assessment of diastolic function. In this review, we summarize the underlying principles of diastolic function, dividing diastole into two phases: 1) relaxation and 2) filling. We identify parameters used to comprehensively evaluate diastolic function by hemodynamics, clarify how each parameter is obtained, and consider the advantages and limitations associated with each measure. We provide a summary of the sensitivity of each diastolic parameter to loading conditions. Furthermore, we discuss differences that can occur in the accuracy of diastolic and systolic indices when generated by automated software compared with custom software analysis and the magnitude each parameter is influenced during inspiration with healthy breathing and a mild breathing load, commonly expected in heart failure. Finally, we identify key variables to control (e.g., body temperature, anesthetic, sampling rate) when collecting hemodynamic data. This review provides fundamental knowledge for users to succeed in troubleshooting and guidelines for evaluating diastolic function by hemodynamics in experimental models of heart failure.
Subject(s)
Blood Pressure , Disease Models, Animal , Heart Failure/physiopathology , Practice Guidelines as Topic , Ventricular Function , Animals , Heart Function Tests/methods , Heart Function Tests/standardsABSTRACT
We present a mathematical model of biofilm response to antibiotics, controlled by a quorum sensing system that confers increased resistance. The model is a highly nonlinear system of partial differential equations that we investigate in computer simulations. Our results suggest that an adaptive, quorum sensing-controlled, mechanism to switch between modes of fast growth with little protection and protective modes of slow growth may confer benefits to biofilm populations. It enhances the formation of micro-niches in the inner regions of the biofilm in which bacteria are not easily reached by antibiotics. Whereas quorum sensing inhibitors can delay the onset of increased resistance, their advantage is lost after up-regulation. This emphasizes the importance of timing for treatment of biofilms with antibiotics.
Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Biofilms/growth & development , Models, Biological , Quorum Sensing/drug effects , Quorum Sensing/physiology , Acyl-Butyrolactones/metabolism , Bacteria/drug effects , Bacteria/genetics , Bacteria/growth & development , Biomass , Computer Simulation , Drug Resistance, Bacterial/genetics , Drug Resistance, Bacterial/physiology , Gene Expression Regulation, Bacterial , Mathematical Concepts , Nonlinear DynamicsABSTRACT
We incorporate a mathematical model of Varroa destructor and the Acute Bee Paralysis Virus with an existing model for a honeybee colony, in which the bee population is divided into hive bees and forager bees based on tasks performed in the colony. The model is a system of five ordinary differential equations with dependent variables: uninfected hive bees, uninfected forager bees, infected hive bees, virus-free mites and virus-carrying mites. The interplay between forager loss and disease infestation is studied. We study the stability of the disease-free equilibrium of the bee-mite-virus model and observe that the disease cannot be fought off in the absence of varroacide treatment. However, the disease-free equilibrium can be stable if the treatment is strong enough and also if the virus-carrying mites become virus-free at a rate faster than the mite birth rate. The critical forager loss due to homing failure, above which the colony fails, is calculated using simulation experiments for disease-free, treated and untreated mite-infested, and treated virus-infested colonies. A virus-infested colony without varroacide treatment fails regardless of the forager mortality rate.
Subject(s)
Bees , Dicistroviridae/pathogenicity , Feeding Behavior , Models, Theoretical , Animals , Population Dynamics , VarroidaeABSTRACT
We analyze a mathematical model of quorum sensing induced biofilm dispersal. It is formulated as a system of non-linear, density-dependent, diffusion-reaction equations. The governing equation for the sessile biomass comprises two non-linear diffusion effects, a degeneracy as in the porous medium equation and fast diffusion. This equation is coupled with three semi-linear diffusion-reaction equations for the concentrations of growth limiting nutrients, autoinducers, and dispersed cells. We prove the existence and uniqueness of bounded non-negative solutions of this system and study the behavior of the model in numerical simulations, where we focus on hollowing effects in established biofilms.
Subject(s)
Biofilms , Models, Biological , Quorum Sensing , Biomass , Computer SimulationABSTRACT
We present a mathematical model (a) for the infection of a honey bee colony with Nosema ceranae. This is a system of five ordinary differential equations for the dependent variables healthy and infected worker bees in the hive, healthy and infected forager bees, and disease potential deposited in the hive. The model is then (b) extended to account for increased forager losses, e.g. caused by exposure to external stressors. The model is non-autonomous with periodic coefficient functions. Algebraic complexity prevents a rigorous mathematical analysis. Therefore, we resort to computer simulations in addition to some analytical results in the constant coefficient case. We investigate each of the two stressors (a) and (b) individually and jointly. Our results indicate that the combined effect of two stressors, both of which can be tolerated by the colony individually, might lead to colony failure, suggesting multi-factorial causes behind losses of honey bee colonies.
Subject(s)
Bees/parasitology , Models, Biological , Nosema/pathogenicity , Animals , Stress, PhysiologicalABSTRACT
We study a previously introduced mathematical model of amensalistic control of the foodborne pathogen Listeria monocytogenes by the generally regarded as safe lactic acid bacteria Lactococcus lactis in a chemostat setting under nutrient rich growth conditions. The control agent produces lactic acids and thus affects pH in the environment such that it becomes detrimental to the pathogen while it is much more tolerant to these self-inflicted environmental changes itself. The mathematical model consists of five nonlinear ordinary differential equations for both bacterial species, the concentration of lactic acids, the pH and malate. The model is algebraically too involved to allow a comprehensive, rigorous qualitative analysis. Therefore, we conduct a computational study. Our results imply that depending on the growth characteristics of the medium in which the bacteria are cultured, the pathogen can survive in an intermediate flow regime but will be eradicated for slower flow rates and washed out for higher flow rates.
ABSTRACT
A spatially continuous mathematical model of transport processes, anaerobic digestion and microbial complexity as would be expected in the human colon is presented. The model is a system of first-order partial differential equations with context determined number of dependent variables, and stiff, non-linear source terms. Numerical simulation of the model is used to elucidate information about the colon-microbiota complex. It is found that the composition of materials on outflow of the model does not well-describe the composition of material in other model locations, and inferences using outflow data varies according to model reactor representation. Additionally, increased microbial complexity allows the total microbial community to withstand major system perturbations in diet and community structure. However, distribution of strains and functional groups within the microbial community can be modified depending on perturbation length and microbial kinetic parameters. Preliminary model extensions and potential investigative opportunities using the computational model are discussed.
Subject(s)
Colon/microbiology , Dietary Carbohydrates/metabolism , Digestion , Intestinal Absorption , Microbiota , Models, Theoretical , Colon/metabolism , Fermentation , HumansABSTRACT
We propose a deterministic continuum model for mixed-culture biofilms. A crucial aspect is that movement of one species is affected by the presence of the other. This leads to a degenerate cross-diffusion system that generalizes an earlier single-species biofilm model. Two derivations of this new model are given. One, like cellular automata biofilm models, starts from a discrete in space lattice differential equation where the spatial interaction is described by microscopic rules. The other one starts from the same continuous mass balances that are the basis of other deterministic biofilm models, but it gives up a simplifying assumption of these models that has recently been criticized as being too restrictive in terms of ecological structure. We show that both model derivations lead to the same PDE model, if corresponding closure assumptions are introduced. To investigate the role of cross-diffusion, we conduct numerical simulations of three biofilm systems: competition, allelopathy and a mixed system formed by an aerobic and an anaerobic species. In all cases, we find that accounting for cross-diffusion affects local distribution of biomass, but it does not affect overall lumped quantities such as the total amount of biomass in the system.
Subject(s)
Biofilms/growth & development , Models, Biological , Biomass , Computer Simulation , Diffusion , Mathematical Concepts , Nonlinear DynamicsABSTRACT
A mathematical model for the honeybee-varroa mite-ABPV system is proposed in terms of four differential equations for the: infected and uninfected bees in the colony, number of mites overall, and of mites carrying the virus. To account for seasonal variability, all parameters are time periodic. We obtain linearized stability conditions for the disease-free periodic solutions. Numerically, we illustrate that, for appropriate parameters, mites can establish themselves in colonies that are not treated with varroacides, leading to colonies with slightly reduced number of bees. If some of these mites carry the virus, however, the colony might fail suddenly after several years without a noticeable sign of stress leading up to the failure. The immediate cause of failure is that at the end of fall, colonies are not strong enough to survive the winter in viable numbers. We investigate the effect of the initial disease infestation on collapse time, and how varroacide treatment affects long-term behavior. We find that to control the virus epidemic, the mites as disease vector should be controlled.
Subject(s)
Bees/parasitology , Varroidae/pathogenicity , Animals , Arachnid Vectors/pathogenicity , Arachnid Vectors/virology , Bees/virology , Computer Simulation , Dicistroviridae/pathogenicity , Ectoparasitic Infestations/parasitology , Ectoparasitic Infestations/veterinary , Mathematical Concepts , Models, Biological , Seasons , Varroidae/virologyABSTRACT
BACKGROUND: Cell dispersal (or detachment) is part of the developmental cycle of microbial biofilms. It can be externally or internally induced, and manifests itself in discrete sloughing events, whereby many cells disperse in an instance, or in continuous slower dispersal of single cells. One suggested trigger of cell dispersal is quorum sensing, a cell-cell communication mechanism used to coordinate gene expression and behavior in groups based on population densities. METHOD: To better understand the interplay of colony growth and cell dispersal, we develop a dynamic, spatially extended mathematical model that includes biofilm growth, production of quorum sensing molecules, cell dispersal triggered by quorum sensing molecules, and re-attachment of cells. This is a highly nonlinear system of diffusion-reaction equations that we study in computer simulations. RESULTS: Our results show that quorum sensing induced cell dispersal can be an efficient mechanism for bacteria to control the size of a biofilm colony, and at the same time enhance its downstream colonization potential. In fact we find that over the lifetime of a biofilm colony the majority of cells produced are lost into the aqueous phase, supporting the notion of biofilms as cell nurseries. We find that a single quorum sensing based mechanism can explain both, discrete dispersal events and continuous shedding of cells from a colony. Moreover, quorum sensing induced cell dispersal affects the structure and architecture of the biofilm, for example it might lead to the formation of hollow inner regions in a biofilm colony.
Subject(s)
Bacterial Adhesion , Biofilms/growth & development , Models, Biological , Quorum Sensing , Biomass , Computer Simulation , Numerical Analysis, Computer-Assisted , Time FactorsABSTRACT
We investigate the question of optimal substrate removal in a biofilm reactor with concurrent suspended growth, both with respect to the amount of substrate removed and with respect to treatment process duration. The water to be treated is fed externally from a buffer vessel to the treatment reactor. In the two-objective optimal control problem, the flow rate between the vessels is selected as the control variable. The treatment reactor is modelled by a system of three ordinary differential equations in which a two-point boundary value problem is embedded. The solution of the associated singular optimal control problem in the class of measurable functions is impractical to determine and infeasible to implement in real reactors. Instead, we solve the simpler problem to optimize reactor performance in the class of off-on functions, a choice that is motivated by the underlying biological process. These control functions start with an initial no-flow period and then switch to a constant flow rate until the buffer vessel is empty. We approximate the Pareto Front numerically and study the behaviour of the system and its dependence on reactor and initial data. Overall, the modest potential of control strategies to improve reactor performance is found to be primarily due to an initial transient period in which the bacteria have to adapt to the environmental conditions in the reactor, i.e. depends heavily on the initial state of the dynamic system. In applications, the initial state, however, is often unknown and therefore the efficiency of reactor optimization, compared to the uncontrolled system with constant flow rate, is limited.
Subject(s)
Bacteria/growth & development , Biofilms/growth & development , Bioreactors/microbiology , Models, Biological , Bacterial Physiological PhenomenaABSTRACT
Many biological wastewater treatment processes are based on bacterial biofilms, i.e. layered aggregates of microbial populations deposited on surfaces. Detachment and (re-)attachment leads to an exchange of biomass between the biofilm and the surrounding aqueous phase. Traditionally, mathematical models of biofilm processes do not take the contribution of the suspended, non-attached bacteria into account, implicitly assuming that these are negligible due to the relatively small amount of suspended biomass compared to biofilm biomass. In this paper, we present a model for a nitrifying biofilm reactor that explicitly includes both types of biomass. The model is derived by coupling a reactor mass balance for suspended populations and substrates with a full one-dimensional Wanner-Gujer type biofilm model. The complexity of this model, both with respect to mathematical structure and number of parameters, prevents a rigorous analysis of its dynamics, wherefore we study the model numerically.Our investigations show that suspended biomass needs to be considered explicitly in the model if the interests of the study are the details of the nitrification process and its intermediate steps and compounds. However, suspended biomass may be neglected if the primary interests are the overall reactor performance criteria, such as removal rates. Furthermore, it can be expected that changes in the biofilm area, attachment, detachment, and dilution rates are more likely to affect the variables primarily associated with the second step of nitrification, while the variables associated with the first step tend to be more robust.