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先进的牙菌斑生物膜模型:pH值在预测定植中的重要作用

Advancing dental biofilm models: the integral role of pH in predicting colonization.

作者信息

Sangha Jay S, Gogulancea Valentina, Curtis Thomas P, Jakubovics Nicholas S, Barrett Paul, Metris Aline, Ofiţeru Irina D

机构信息

School of Engineering, Newcastle University, Newcastle upon Tyne, United Kingdom.

Faculty of Medical Sciences, Newcastle University, School of Dental Sciences, Newcastle upon Tyne, United Kingdom.

出版信息

mSphere. 2025 Jan 28;10(1):e0074324. doi: 10.1128/msphere.00743-24. Epub 2024 Dec 11.

Abstract

Mathematical models can provide insights into complex interactions and dynamics within microbial communities to complement and extend experimental laboratory approaches. For dental biofilms, they can give a basis for evaluating biofilm growth or the transition from health to disease. We have developed mathematical models to simulate the transition toward a cariogenic microbial biofilm, modeled as the overgrowth of within a five-species dental community. This work builds on experimental data from a continuous flow reactor with hydroxyapatite coupons for biofilm growth, in a chemically defined medium with varying concentrations of glucose and lactic acid. The biofilms formed on the coupons were simulated using individual-based models (IbMs), with bacterial growth modeled using experimentally measured kinetic parameters. The IbM assumes that the maximum theoretical growth yield for biomass is dependent on the local concentration of reactants and products, while the growth rates were described using traditional Monod equations. We have simulated all the conditions studied experimentally, considering different initial relative abundance of the five species, and also different initial clustering in the biofilm. The simulation results only reproduced the experimental dominance of at high glucose concentration after we considered the species-specific effect of pH on growth rates. This highlights the significance of the aciduric property of in the development of caries. Our study demonstrates the potential of combining and studies to gain a new understanding of the factors that influence dental biofilm dynamics.IMPORTANCEWe have developed models able to reproduce the relative abundance measured in the synthetic dental biofilm communities growing in a chemically defined medium. The advantage of this combination of and models is that we can study the influence of one parameter at a time and aim for direct validation. Our work demonstrates the utility of individual-based models for simulating diverse conditions affecting dental biofilm scenarios, such as the frequency of glucose intake, sucrose pulsing, or integration of pathogenic or probiotic species. Although models are reductionist approaches, they have the advantage of not being limited in the scenarios they can test by the ethical consideration of an system, thus significantly contributing to dental biofilm research.

摘要

数学模型可以深入了解微生物群落内的复杂相互作用和动态变化,以补充和扩展实验室内的研究方法。对于牙菌斑生物膜而言,数学模型可为评估生物膜生长或从健康状态向疾病状态的转变提供依据。我们开发了数学模型来模拟向致龋微生物生物膜的转变,该生物膜被建模为五种细菌构成的牙菌斑群落中某种细菌的过度生长。这项工作基于连续流动反应器的实验数据,该反应器带有用于生物膜生长的羟基磷灰石试片,处于含有不同浓度葡萄糖和乳酸的化学限定培养基中。使用基于个体的模型(IbMs)对试片上形成的生物膜进行模拟,细菌生长则使用实验测量的动力学参数进行建模。IbM假设生物量的最大理论生长产量取决于反应物和产物的局部浓度,而生长速率则使用传统的莫诺德方程来描述。我们模拟了所有实验研究的条件,考虑了五种细菌不同的初始相对丰度以及生物膜中不同的初始聚集情况。只有在我们考虑了pH对生长速率的物种特异性影响之后,模拟结果才重现了高葡萄糖浓度下某种细菌在实验中的优势地位。这突出了该细菌的耐酸性在龋齿发展中的重要性。我们的研究证明了将实验和模拟研究相结合以重新理解影响牙菌斑生物膜动态变化因素的潜力。重要性我们开发了能够重现化学限定培养基中生长的合成牙菌斑生物膜群落中测量到的相对丰度的模型。这种实验和模拟模型相结合的优势在于我们可以一次研究一个参数的影响,并旨在进行直接验证。我们的工作证明了基于个体的模型在模拟影响牙菌斑生物膜情况的各种条件方面的实用性,例如葡萄糖摄入频率、蔗糖脉冲或致病或益生菌种的整合。尽管模拟模型是简化方法,但它们的优势在于不受伦理因素对实验系统限制的影响,从而能在可测试的场景中不受限制,因此对牙菌斑生物膜研究有重大贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8d0/11774048/f6513a59141c/msphere.00743-24.f001.jpg

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