Human gut microbiota evaluation and comparation after the separate or combined antibiotics exposure using the simulator of human intestinal microbial ecosystem (SHIME)

Abstract Background A cocktail of drugs is an emerging toxic contaminant that has potential public health risk worldwide, which also would cause human intestinal microbial disorder and develop multiple human diseases. However, to date, the combination effects of antibiotics cocktail on human intestinal microbiota dysbiosis and related health risk are not fully understood. Therefore, for the first time, this study evaluated and compared the in vitro ability of amoxicillin (AMX) and polymyxin E (POL) used separately or combined on antibiotic resistance genes (ARGs) as well as human disease-related pathways in the simulated human gut. Results This study indicated that the combination exposure of POL with AMX reduced the occurrence of drug resistance in the gut microbiota caused by single antibiotic treatment. However, in comparison with the separate use of AMX and POL, the combined treatment exhibited a significantly higher ability to increase the human disease-related pathways. The combination effects on genetic level might attribute to microbiota shift, as co-occurrence patterns suggested that Bifidobacterium attributed to ARGs increasing in the POL treatment group and Enterobacter played a crucial role in human disease-related pathways enrichment after combination treatment. Conclusion These results may open up new perspectives for assessing the direct effects of combination antibiotics on the intestinal microbiota. These suggested side-effects should be considered for a combination of antibiotics prescription.