Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden.
Departamento de Ingeniería de Procesos e Hidráulica, Universidad Autónoma Metropolitana-Iztapalapa, 09340 Ciudad de México, México.
Proc Natl Acad Sci U S A. 2021 Mar 30;118(13). doi: 10.1073/pnas.2019336118.
Microbial variations in the human gut are harbored in temporal and spatial heterogeneity, and quantitative prediction of spatiotemporal dynamic changes in the gut microbiota is imperative for development of tailored microbiome-directed therapeutics treatments, e.g. precision nutrition. Given the high-degree complexity of microbial variations, subject to the dynamic interactions among host, microbial, and environmental factors, identifying how microbiota colonize in the gut represents an important challenge. Here we present COmputing the DYnamics of microbiota (CODY), a multiscale framework that integrates species-level modeling of microbial dynamics and ecosystem-level interactions into a mathematical model that characterizes spatial-specific in vivo microbial residence in the colon as impacted by host physiology. The framework quantifies spatiotemporal resolution of microbial variations on species-level abundance profiles across site-specific colon regions and in feces, independent of a priori knowledge. We demonstrated the effectiveness of CODY using cross-sectional data from two longitudinal metagenomics studies-the microbiota development during early infancy and during short-term diet intervention of obese adults. For each cohort, CODY correctly predicts the microbial variations in response to diet intervention, as validated by available metagenomics and metabolomics data. Model simulations provide insight into the biogeographical heterogeneity among lumen, mucus, and feces, which provides insight into how host physical forces and spatial structure are shaping microbial structure and functionality.
人类肠道中的微生物变化存在时间和空间异质性，定量预测肠道微生物群的时空动态变化对于开发针对微生物组的治疗方法至关重要，例如精准营养。鉴于微生物变化的高度复杂性，受到宿主、微生物和环境因素之间的动态相互作用的影响，确定微生物如何在肠道中定植是一个重要的挑战。在这里，我们提出了计算微生物动态（CODY），这是一个多尺度框架，将微生物动态的物种水平建模和生态系统水平的相互作用整合到一个数学模型中，该模型描述了宿主生理学对结肠中体内微生物定植的空间特异性。该框架量化了物种水平丰度谱上的时空分辨率微生物变化，跨越特定于部位的结肠区域和粪便，而无需先验知识。我们使用来自两项纵向宏基因组学研究的横断面数据（婴儿早期和肥胖成年人短期饮食干预期间的微生物组发育）证明了 CODY 的有效性。对于每个队列，CODY 都正确预测了饮食干预后的微生物变化，这可以通过可用的宏基因组学和代谢组学数据来验证。模型模拟提供了对腔、粘液和粪便之间生物地理异质性的深入了解，这为宿主物理力和空间结构如何塑造微生物结构和功能提供了线索。
