(645c) The Arginine Dihydrolase Pathway Shapes Human Gut Community Assembly and Functions

The human gut microbiome substantially expands our genome’s capabilities by encoding numerous specialized metabolic pathways. These specialized metabolic pathways are harbored by distinct taxa and contribute uniquely to the functions performed by the gut microbiota. Understanding specialized metabolic pathways’ contribution to community-level interactions present accessible strategies for microbiome engineering. The arginine dihydrolase metabolic pathway (arc operon) is a specialized metabolic pathway present in the genomes of diverse human gut bacterial species and can modulate environmental pH. We investigated the role of the arc operon in the probiotic E. coli Nissle on the assembly and production of the beneficial metabolite butyrate in a human gut community in vitro and in the murine gut. The presence of the arc operon shapes the dynamics of community assembly. With arc operon expression, we observed reduced variability in community structure from environmental pH perturbations. In particular, the abundance of butyrate producers was altered either transiently or permanently. The arc operon can enhance or reduce butyrate production depending on the environmental pH. Dynamic computational modeling of community assembly reveals the extent of pH-mediated inter-species interactions on community assembly. Several species are identified with significant beneficial or detrimental non-pH-mediated interactions. Overall, we demonstrate that a single specialized metabolic pathway can shape community assembly, species colonization of the mammalian gut, and metabolite production. Hence, they are promising engineering targets for therapeutics design and bioproduct manufacturing.

Paper for this research: Liu, Y. et al. The arginine dihydrolase pathway shapes human gut microbial community assembly, functions, and mammalian host colonization. bioRxiv 2023.01.10.523442 (2023) doi:10.1101/2023.01.10.523442.