Horizontal Transfer Mediated Proliferation of Antibiotic Resistance Genes in High-Fat Diet Induced Obesity Mice

Background Infections caused by pathogens carrying antibiotic resistance genes (ARGs) are triggering a global health crisis. Human gut microbiota is an important reservoir of ARGs, which can not only be exchanged inside the symbiotic microbiota, but can also be horizontally transferred to opportunistic pathogens. A dysbiotic gut microbiota has been associated with obesity and other metabolic disorders, which has also been described as the most unneglected global health problem. Many studies have focused on the effects of antibiotics and other exogenous chemical on the fate of ARGs, but little is known about the effect of obesity induced dysbiotic gut microbiota on the fate of ARGs. Results This study addressed the significant proliferation of ARGs and the dramatical change of mobile genetic elements (MGEs) in high-fat diet induced obesity (DIO) mice, which the ermB and tnpA-03 genes mostly increased, demonstrating that DIO alone could enrich the abundance of ARGs. A clear increase of serine and tyrosine in the feces showed a significant positive correlation with the dominant genes of DIO groups (ermB and tnpA-03), suggesting that serine and tyrosine might enhance DNA transposition (tnpA-03) by nucleophilic attacking a phosphorus atom of a backbone phosphate group and ultimately significantly amplified the ARGs. Additionally, ermB has been frequently found in obesity-associated Lactobacillus, which might contribute to the sharp increase of ARGs and dramatical change of MGEs in the DIO mice. Finally, procrustes analysis showed the explanatory variables of the MGEs, the metabolites, and the microbial communities for the ARGs accounted for 94.3%, 53.4%, and 68.1%, respectively. Conclusion This study demonstrated that DIO significantly enhanced the abundance of ARGs and dramatically changed MGEs in mouse gut microbiota. MGEs were the most direct factor affecting ARGs, and microbiota were the main driver of the proliferation of ARGs in the DIO mice.