Department of Environmental & Occupational Health Sciences, University of Washington, Seattle, WA, 98105, USA.
Institute for Systems Biology, Seattle, WA, 98109, USA.
Nat Commun. 2023 Sep 14;14(1):5682. doi: 10.1038/s41467-023-41424-1.
Longitudinal sampling of the stool has yielded important insights into the ecological dynamics of the human gut microbiome. However, human stool samples are available approximately once per day, while commensal population doubling times are likely on the order of minutes-to-hours. Despite this mismatch in timescales, much of the prior work on human gut microbiome time series modeling has assumed that day-to-day fluctuations in taxon abundances are related to population growth or death rates, which is likely not the case. Here, we propose an alternative model of the human gut as a stationary system, where population dynamics occur internally and the bacterial population sizes measured in a bolus of stool represent a steady-state endpoint of these dynamics. We formalize this idea as stochastic logistic growth. We show how this model provides a path toward estimating the growth phases of gut bacterial populations in situ. We validate our model predictions using an in vitro Escherichia coli growth experiment. Finally, we show how this method can be applied to densely-sampled human stool metagenomic time series data. We discuss how these growth phase estimates may be used to better inform metabolic modeling in flow-through ecosystems, like animal guts or industrial bioreactors.
对粪便进行纵向采样,使人们深入了解人类肠道微生物组的生态动力学。然而,人类粪便样本大约每天只能获得一次,而共生种群的倍增时间可能在几分钟到几小时之间。尽管时间尺度不匹配,但在人类肠道微生物组时间序列建模的先前大部分工作中,都假设分类群丰度的日常波动与种群增长率或死亡率有关,但事实可能并非如此。在这里,我们提出了一种替代模型,将人类肠道视为一个静止系统,其中种群动态发生在内部,粪便中测量的细菌种群大小代表这些动态的稳态终点。我们将这个想法形式化为随机逻辑增长。我们展示了如何使用这种模型来估计肠道细菌种群的生长阶段。我们使用体外大肠杆菌生长实验验证了我们的模型预测。最后,我们展示了如何将这种方法应用于密集采样的人类粪便宏基因组时间序列数据。我们讨论了这些生长阶段估计值如何用于更好地为流动生态系统(如动物肠道或工业生物反应器)中的代谢建模提供信息。