Stochastic models of the chemostat

We consider the modeling of the dynamics of the chemostat at its very source. The chemostat is classically represented as a system of ordinary differential equations. Our goal is to establish a stochastic model that is valid at the scale immediately preceding the one corresponding to the deterministic model. At a microscopic scale we present a pure jump stochastic model that gives rise, at the macroscopic scale, to the ordinary differential equation model. At an intermediate scale, an approximation diffusion allows us to propose a model in the form of a system of stochastic differential equations. We expound the mechanism to switch from one model to another, together with the associated simulation procedures. We also describe the domain of validity of the different models

Model Systems of Human Intestinal Flora, to Set Acceptable Daily Intakes of Antimicrobial Residues

The veterinary use of antimicrobial drugs in food producing animals may result in residues in food, that might modify the consumer gut flora. This review compares three model systems that maintain a complex flora of human origin: (i) human flora associated (HFA) continuous flow cultures in chemostats, (ii) HFA mice, and (iii) human volunteers. The "No Microbial Effect Level" of an antibiotic on human flora, measured in one of these models, is used to set the accept¬able daily intake (ADI) for human consumers. Human volunteers trials are most relevant to set microbio¬log¬ical ADI, and may be considered as the "gold standard". However, human trials are very expensive and unethical. HFA chemostats are controlled systems, but tetracycline ADI calculated from a chemostat study is far above result of a human study. HFA mice studies are less expensive and better controlled than human trials. The tetracycline ADI derived from HFA mice studies is close to the ADI directly obtained in human volunteers

Stochastic analysis of a full system of two competing populations in a chemostat

This paper formulates two 3D stochastic differential equations (SDEs) of two microbial populations in a chemostat competing over a single substrate. The two models have two distinct noise sources. One is general noise whereas the other is dilution rate induced noise. Nonlinear Monod growth rates are assumed and the paper is mainly focused on the parameter values where coexistence is present deterministically. Nondimensionalising the equations around the point of intersection of the two growth rates leads to a large parameter which is the nondimensional substrate feed. This in turn is used to perform an asymptotic analysis leading to a reduced 2D system of equations describing the dynamics of the populations on and close to a line of steady states retrieved from the deterministic stability analysis. That reduced system allows the formulation of a spatially 2D Fokker-Planck equation which when solved numerically admits results similar to those from simulation of the SDEs. Contrary to previous suggestions, one particular population becomes dominant at large times. Finally, we brie y explore the case where death rates are added

Universal protein fluctuations in populations of microorganisms

The copy number of any protein fluctuates among cells in a population; characterizing and understanding these fluctuations is a fundamental problem in biophysics. We show here that protein distributions measured under a broad range of biological realizations collapse to a single non-Gaussian curve under scaling by the first two moments. Moreover in all experiments the variance is found to depend quadratically on the mean, showing that a single degree of freedom determines the entire distribution. Our results imply that protein fluctuations do not reflect any specific molecular or cellular mechanism, and suggest that some buffering process masks these details and induces universality

Irreversible thermodynamics of open chemical networks I: Emergent cycles and broken conservation laws

In this and a companion paper we outline a general framework for the thermodynamic description of open chemical reaction networks, with special regard to metabolic networks regulating cellular physiology and biochemical functions. We first introduce closed networks "in a box", whose thermodynamics is subjected to strict physical constraints: the mass-action law, elementarity of processes, and detailed balance. We further digress on the role of solvents and on the seemingly unacknowledged property of network independence of free energy landscapes. We then open the system by assuming that the concentrations of certain substrate species (the chemostats) are fixed, whether because promptly regulated by the environment via contact with reservoirs, or because nearly constant in a time window. As a result, the system is driven out of equilibrium. A rich algebraic and topological structure ensues in the network of internal species: Emergent irreversible cycles are associated to nonvanishing affinities, whose symmetries are dictated by the breakage of conservation laws. These central results are resumed in the relation $a + b = s^Y$ between the number of fundamental affinities $a$, that of broken conservation laws $b$ and the number of chemostats $s^Y$. We decompose the steady state entropy production rate in terms of fundamental fluxes and affinities in the spirit of Schnakenberg's theory of network thermodynamics, paving the way for the forthcoming treatment of the linear regime, of efficiency and tight coupling, of free energy transduction and of thermodynamic constraints for network reconstruction.Comment: 18 page

Global dynamics of the chemostat with variable yields

In this paper, we consider a competition model between $n$ species in a chemostat including both monotone and non-monotone response functions, distinct removal rates and variable yields. We show that only the species with the lowest break-even concentration survives, provided that additional technical conditions on the growth functions and yields are satisfied. LaSalle's extension theorem of the Lyapunov stability theory is the main tool.Comment: 7 page