Journal of South China University of Technology(Natural Science) >
Effects of Bupropion Hydrochloride on Resistome of Gut Microbiota in SD Rats
Received date: 2024-05-27
Online published: 2024-11-26
Supported by
the National Natural Science Foundation of China(32170064)
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.
YAN He , CHEN Chunxia , LIU Zongbao , LI Jialin , ZHAN Shimin . Effects of Bupropion Hydrochloride on Resistome of Gut Microbiota in SD Rats[J]. Journal of South China University of Technology(Natural Science), 2025 , 53(10) : 155 -173 . DOI: 10.12141/j.issn.1000-565X.240258
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