Department of Physics, University of California, San Diego, La Jolla, CA 92093-0374
Proc Natl Acad Sci U S A. 2017 Jun 20;114(25):6438-6443. doi: 10.1073/pnas.1619598114. Epub 2017 Jun 6.
The human gut harbors a dynamic microbial community whose composition bears great importance for the health of the host. Here, we investigate how colonic physiology impacts bacterial growth, which ultimately dictates microbiota composition. Combining measurements of bacterial physiology with analysis of published data on human physiology into a quantitative, comprehensive modeling framework, we show how water flow in the colon, in concert with other physiological factors, determine the abundances of the major bacterial phyla. Mechanistically, our model shows that local pH values in the lumen, which differentially affect the growth of different bacteria, drive changes in microbiota composition. It identifies key factors influencing the delicate regulation of colonic pH, including epithelial water absorption, nutrient inflow, and luminal buffering capacity, and generates testable predictions on their effects. Our findings show that a predictive and mechanistic understanding of microbial ecology in the gut is possible. Such predictive understanding is needed for the rational design of intervention strategies to actively control the microbiota.
人类肠道中栖息着一个动态的微生物群落，其组成对于宿主的健康至关重要。在这里，我们研究了结肠生理学如何影响细菌生长，而细菌生长最终决定了微生物群落的组成。我们将细菌生理学的测量结果与关于人体生理学的已发表数据的分析结合到一个定量的、全面的建模框架中，展示了结肠中的水流如何与其他生理因素一起决定了主要细菌门的丰度。从机制上讲，我们的模型表明，腔中的局部 pH 值（其对不同细菌的生长有不同的影响）驱动着微生物群落组成的变化。它确定了影响结肠 pH 值精细调节的关键因素，包括上皮细胞的水分吸收、营养物质的流入和腔的缓冲能力，并对它们的影响提出了可验证的预测。我们的研究结果表明，对肠道微生物生态学进行预测和机制理解是可能的。这种预测性的理解对于合理设计干预策略以主动控制微生物群是必要的。
