Bacterial growth often alters the environment, which in turn can impact interspecies interactions among bacteria. Here, we used an in vitro batch system containing mucin beads to emulate the dynamic host environment and to study its impact on the interactions between two abundant and prevalent human gut bacteria, the primary fermenter Bacteroides thetaiotaomicron and the butyrate producer Roseburia intestinalis. By combining machine learning and flow cytometry, we found that the number of viable B. thetaiotaomicron cells decreases with glucose consumption due to acid production, while R. intestinalis survives post-glucose depletion by entering a slow growth mode. Both species attach to mucin beads, but only viable cell counts of B. thetaiotaomicron increase significantly. The number of viable co-culture cells varies significantly over time compared to those of monocultures. A combination of targeted metabolomics and RNA-seq showed that the slow growth mode of R. intestinalis represents a diauxic shift towards acetate and lactate consumption, whereas B. thetaiotaomicron survives glucose depletion and low pH by foraging on mucin sugars. In addition, most of the mucin monosaccharides we tested inhibited the growth of R. intestinalis but not B. thetaiotaomicron. We encoded these causal relationships in a kinetic model, which reproduced the observed dynamics. In summary, we explored how R. intestinalis and B. thetaiotaomicron respond to nutrient scarcity and how this affects their dynamics. We highlight the importance of understanding bacterial metabolic strategies to effectively modulate microbial dynamics in changing conditions.

细菌的生长常常会改变环境，进而影响细菌之间的种间相互作用。在这里，我们使用含有粘蛋白珠的体外批量系统来模拟动态宿主环境，并研究其对两种丰富且普遍的人类肠道细菌（初级发酵菌Bacteroides thetaiotaomicron和丁酸生产者Roseburia Enteris）之间相互作用的影响。通过结合机器学习和流式细胞术，我们发现，由于酸的产生，存活的B.thetaiotaomicron细胞的数量随着葡萄糖消耗而减少，而R.intestinalis通过进入缓慢的生长模式在葡萄糖消耗后存活下来。两个物种都附着在粘蛋白珠上，但只有B. thetaiotaomicron的活细胞计数显着增加。与单一培养物相比，存活的共培养细胞的数量随时间变化显着。靶向代谢组学和 RNA-seq 的结合表明， R. Enteris的缓慢生长模式代表了向乙酸盐和乳酸消耗的双峰转变，而B. thetaiotaomicron通过以粘蛋白糖为食，在葡萄糖耗尽和低 pH 值下生存。此外，我们测试的大多数粘蛋白单糖抑制肠杆菌的生长，但不抑制多形拟杆菌的生长。我们将这些因果关系编码在动力学模型中，该模型再现了观察到的动力学。总之，我们探讨了R. Enteris和B. thetaiotaomicron如何应对营养缺乏以及这如何影响它们的动态。我们强调了解细菌代谢策略以在不断变化的条件下有效调节微生物动态的重要性。