论文标题
皮肤微生物组模型中的稳定性与元稳定性
Stability versus Meta-stability in a Skin Microbiome Model
论文作者
论文摘要
皮肤微生物组在维持健康皮肤中起着重要作用。它是一个由几种物种组成的生态系统,争夺资源并与皮肤细胞相互作用。皮肤微生物组的失衡,也称为营养不良,与多种皮肤疾病有关,包括痤疮和特应性皮炎。通常,营养不良与一系列机会性致病细菌群(例如,痤疮的痤疮或特应性皮炎的金黄色葡萄球菌)与皮肤的定植有关。由非特异性消除皮肤菌群组成的处理显示出矛盾的结果。因此,有必要了解影响皮肤微生物组组成转移的因素。在这项工作中,我们介绍了基于普通微分方程的数学模型,其中2种类型的细菌种群(皮肤共生和机会性病原体)研究了推动一个人群优势越过另一个人群的机制。通过使用已公开的实验数据,假定与模型中稳定状态的观察相对应,我们得出了限制因素,使我们能够将模型的参数数量从13减少到5。有趣的是,在模型中引入细菌后大约2天,在300小时后,稳定的元素在模型引入后大约2天定居。在实验的时间尺度上,我们表明环境的某些变化,例如皮肤表面pH的升高,为机会性病原体种群造成了皮肤出现和定殖的有利条件。这种预测有助于确定涉及微生物组营养不良的皮肤状况的潜在治疗靶标,并质疑元稳定状态在生物学过程数学模型中的重要性。
The skin microbiome plays an important role in the maintenance of a healthy skin. It is an ecosystem, composed of several species, competing for resources and interacting with the skin cells. Imbalance in the cutaneous microbiome, also called dysbiosis, has been correlated with several skin conditions, including acne and atopic dermatitis. Generally, dysbiosis is linked to colonization of the skin by a population of opportunistic pathogenic bacteria (for example C. acnes in acne or S. aureus in atopic dermatitis). Treatments consisting in non-specific elimination of cutaneous microflora have shown conflicting results. It is therefore necessary to understand the factors influencing shifts of the skin microbiome composition. In this work, we introduce a mathematical model based on ordinary differential equations, with 2 types of bacteria populations (skin commensals and opportunistic pathogens) to study the mechanisms driving the dominance of one population over the other. By using published experimental data, assumed to correspond to the observation of stable states in our model, we derive constraints that allow us to reduce the number of parameters of the model from 13 to 5. Interestingly, a meta-stable state settled at around 2 days following the introduction of bacteria in the model, is followed by a reversed stable state after 300 hours. On the time scale of the experiments, we show that certain changes of the environment, like the elevation of skin surface pH, create favorable conditions for the emergence and colonization of the skin by the opportunistic pathogen population. Such predictions help identifying potential therapeutic targets for the treatment of skin conditions involving dysbiosis of the microbiome, and question the importance of meta-stable states in mathematical models of biological processes.