Liu Yiyi, Cheng Yu-Yu, Thompson Jaron, Zhou Zhichao, Vivas Eugenio I, Warren Matthew F, DuClos Julie M, Anantharaman Karthik, Rey Federico E, Venturelli Ophelia S
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Cell Syst. 2025 May 21;16(5):101292. doi: 10.1016/j.cels.2025.101292. Epub 2025 May 7.
The arginine dihydrolase pathway (arc operon) provides a metabolic niche by transforming arginine into metabolic byproducts. We investigate the role of the arc operon in probiotic Escherichia coli Nissle 1917 on human gut community assembly and health-relevant metabolite profiles. By stabilizing environmental pH, the arc operon reduces variability in community composition in response to pH perturbations and frequently enhances butyrate production in synthetic communities. We use a tailored machine learning model for microbiomes to predict community assembly in response to variation in initial media pH and arc operon activity. This model uncovers the pH- and arc operon-dependent interactions shaping community assembly. Human gut species display altered colonization dynamics in response to the arc operon in the murine gut. In sum, our framework to quantify the contribution of a specific pathway to microbial community assembly and metabolite production can reveal new engineering strategies. A record of this paper's transparent peer review process is included in the supplemental information.
精氨酸二水解酶途径（arc操纵子）通过将精氨酸转化为代谢副产物提供了一个代谢生态位。我们研究了arc操纵子在益生菌大肠杆菌Nissle 1917对人类肠道群落组装和健康相关代谢物谱中的作用。通过稳定环境pH值，arc操纵子减少了群落组成对pH值扰动的变异性，并经常增强合成群落中丁酸盐的产生。我们使用一种针对微生物群定制的机器学习模型来预测群落组装对初始培养基pH值和arc操纵子活性变化的响应。该模型揭示了影响群落组装的pH值和arc操纵子依赖性相互作用。人类肠道物种在小鼠肠道中对arc操纵子的反应显示出定植动态的改变。总之，我们用于量化特定途径对微生物群落组装和代谢物产生贡献的框架可以揭示新的工程策略。本文透明同行评审过程的记录包含在补充信息中。
