Intestinal Flora Metabolites Indole-3-butyric Acid and Disodium Succinate Promote IncI2 mcr-1-carrying Plasmid Transfer

Xin Lu^1*Jialiang Xu²Mengke Zhang²Yi Yan²Zhe Li^1*

• ¹Chinese Center For Disease Control and Prevention, Beijing, China
• ²School of Light Industry, Beijing Technology and Business University, Beijing, China

Plasmid-driven horizontal transfer of resistance genes in bacterial communities is a major factor in the spread of resistance worldwide. The gut microbiome, teeming with billions of microorganisms, serves as a reservoir for resistance genes. The metabolites of gut microorganisms strongly influence the physiology of their microbial community, but the role of the metabolites in the transfer of resistance genes remains unclear. In this study, we demonstrated that two intestinal flora metabolites, indole-3-butyric acid (IBA) and disodium succinate (DS) at low concentrations, which can also be ingested through diet, enhance the interspecies transfer ratio of IncI2 mcr-1-carrying plasmid in Escherichia coli. At 20 mg/L, the transfer ratios in the presence of IBA or DS increased by 2.5-and 2.7-fold compared to that of the control, respectively. Exposure to this concentration of IBA or DS increased the production of reactive oxygen species (ROS), the SOS response, cell membrane permeability, and plasmid copy number. The transcription of genes of the related pathways and of pilus, ATP, and the type IV secretion system (T4SS) was upregulated. Our findings provide the evidence that exposure to low-dose of gut microbiota metabolites promotes the dissemination of resistance plasmids in gut bacteria, highlighting the potential health risks of microbiota metabolites, particularly those used in the food industry.