To investigate the impact of the antidepressant bupropion hydrochloride on the gut microbiome resistome, this study employed Sprague-Dawley (SD) rats as model organisms. Using both 16S rRNA amplicon sequencing and metagenomic sequencing approaches, it systematically analyzed the drug’s effects on microbial communities and their resistome profiles in both fecal and cecal contents. Furthermore, it conducted comprehensive correlation analyses to elucidate potential relationships between these alterations. The results show that prevalent types of ARGs in the feces and cecum samples include bacitracin, tetracycline, vancomycin, and macrolides-lincomycin-streptogramin (MLS). Compared to the control group (HC), the bupropion hydrochloride gavage intervention group (Bup-PO) shows increased total abundance of bacterial antibiotic resistance genes (ARGs) in both fecal and cecal content samples, with statistically significant differences observed only in fecal samples. In terms of ARG types, the Bup-PO group demonstrates significantly increased relative abundance of six antibiotic resistance gene classes in fecal samples compared to the HC group, including: aminoglycoside resistance genes, bacitracin resistance genes, mupirocin resistance genes, rifamycin resistance genes, tetracycline resistance genes, Vancomycin resistance genes. Notably, the treatment group also shows an expansion in the diversity of vancomycin resistance gene variants. In cecum samples, the Bup-PO group significantly increases the relative abundance of 3 resistance gene types, tetracycline, daunorubicin, and fosfomycin. On ARG subtypes, in fecal samples, compared to the HC group, the Bup-PO group significantly increases the relative abundance of vancomycin (vanAG, vanRI, vanSA, vanSI), tetracycline (tetM, tetO, tet32), bacitracin (bceA, bcrA) and rifampicin (rpoB) resistance genes. In cecum samples, the effect of gavage bupropion on ARGs differs from that in fecal samples, with gavage intervention of bupropion causing fluctuations in the relative abundance of the MLS class of resistance genes, decreasing the abundance of lmrB but increasing the abundance of macB. Concurrently, bupropion hydrochloride intervention via oral gavage significantly increased the relative abundance of tetracycline (tetW) and daunorubicin (drrA) resistance genes. The above results suggest that bupropion intervention has the risk of increasing antibiotic resistance in rat’s gut microbiota. UCG-005 and norank__f__norank__o_Clostridia_UCG-014 are the major bacterial genera of the rat intestinal flora, and correlation analyses suggest that UCG-005 may be a potential host for tetracycline, rifampicin, mupirocin, and bacitracin, vancomycin resistance genes, while norank_f__norank__o_Clostridia_UCG-014 may be a potential bacterial host for daunorubicin resistance genes, and their increase after bupropion intervention may be responsible for the increased abundance of these six types of resistance genes.

The problem of food safety and public health caused by bacterial infection has always been a hot issue of social concern, so it is of great significance and application value to explore a safe and efficient food sterilization technology. X-ray irradiation, a new non-thermal sterilization technology with high penetrability that is safety controllable, has a high linear energy transfer (LET) value and relative biological effect (BRE). However, the mechanism for its inactivation effect on foodborne pathogenic bacteria such as Gram-negative bacteria is rarely reported, which greatly limits its application and development in the field of food microbial safety. In this study, the inactivation effect and mechanism of low-energy X-ray on Salmonella, a common foodborne Gram-negative pathogen, were investigated by transcriptomics in an effort to provide a theoretical basis for the application of low-energy X-ray in food safety control. The influence of X-ray irradiation at doses of 0, 0.1, 0.2, 0.3, 0.4, 0.5 and 0.6 kGy on the survival and sublethal effect of Salmonella was analyzed using plate counting method, the effect of X-ray irradiation on bacterial ultrastructure using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) was examined, and the mechanism of Salmonella inactivation by low-energy X-ray was elucidated by transcriptomic analysis. Results showed that the sub-lethal rate of Salmonella was the highest (99.44%) when exposed to 0.5 kGy of X-rays. Low energy X-ray destroyed the bacterial cell wall and membrane. The transcriptome sequencing results showed that among the 292 differentially expressed genes (DEGs) identified, 214 were up-regulated and 78 were down-regulated. DEGs analysis showed that low energy X-ray irradiation could cause DNA damage and regulate oxidative stress response, amino acid synthesis, energy metabolism, virulence, and transmembrane transport in bacterial cells. These findings suggested that low-energy X-ray irradiation has the potential to inhibit bacterial growth and metabolism of cells and thereby reduce the risk of bacterial infection.