Autor: |
Liu Y; Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison WI 53706.; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706., Cheng YY; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706., Thompson J; Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison WI 53706.; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706., Zhou Z; Department of Bacteriology, University of Wisconsin-Madison, WI 53706., Vivas EI; Department of Bacteriology, University of Wisconsin-Madison, WI 53706.; Gnotobiotic Animal Core Facility, University of Wisconsin-Madison, Madison, WI 53706, USA., Warren MF; Department of Bacteriology, University of Wisconsin-Madison, WI 53706., Rey FE; Department of Bacteriology, University of Wisconsin-Madison, WI 53706., Anantharaman K; Department of Bacteriology, University of Wisconsin-Madison, WI 53706., Venturelli OS; Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison WI 53706.; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706.; Department of Bacteriology, University of Wisconsin-Madison, WI 53706. |
Abstrakt: |
The arginine dihydrolase pathway ( arc operon) present in a subset of diverse human gut species enables arginine catabolism. This specialized metabolic pathway can alter environmental pH and nitrogen availability, which in turn could shape gut microbiota inter-species interactions. By exploiting synthetic control of gene expression, we investigated the role of the arc operon in probiotic Escherichia coli Nissle 1917 on human gut community assembly and health-relevant metabolite profiles in vitro and in the murine gut. By stabilizing environmental pH, the arc operon reduced variability in community composition across different initial pH perturbations. The abundance of butyrate producing bacteria were altered in response to arc operon activity and butyrate production was enhanced in a physiologically relevant pH range. While the presence of the arc operon altered community dynamics, it did not impact production of short chain fatty acids. Dynamic computational modeling of pH-mediated interactions reveals the quantitative contribution of this mechanism to community assembly. In sum, our framework to quantify the contribution of molecular pathways and mechanism modalities on microbial community dynamics and functions could be applied more broadly. |