关键词: 抗抑郁药, 肠道菌群, 抗生素耐药性, 宏基因组学

Abstract:

SD rats (Sprague Dawley rats) were selected as the research object to investigate the effect of bupropion, an antidepressant, on the antibiotic resistance of gut microbiota. 16S rRNA high-throughput sequencing and metagenomic sequencing technology were used to analyze the effect of bupropion on the gut microbiota and its resistome of rats' fecal and cecal contents and explore the association between them. The results showed that prevalent types of ARGs in the feces and cecum samples included bacitracin, tetracycline, vancomycin, and macrolides-lincomycin-streptogramin (MLS). Bupropion gavage intervention significantly affected rats' total ARG abundance, beta diversity, ARG types, and ARG subtypes of resistome. Gavage administration of bupropion (Bup-PO) increased total ARG abundance in rat feces and cecum contents samples compared to the control (HC) group, but a significant difference was reached only in fecal samples. In terms of ARG types, compared to the HC group, the Bup-PO group significantly increased the relative abundance of 6 ARG types including aminoglycoside, bacitracin, mupirocin, rifamycin, tetracycline, and vancomycin in fecal samples，and also increased the number of vancomycin-resistant genes. In cecum samples, the Bup-PO group significantly increased 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 increased 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 differed from that in fecal samples, with gavage administration 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. Also, gavage administration of bupropion 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 administration may be responsible for the increased abundance of these six types of resistance genes.

Key words: antidepressants, gut microbiota; antibiotic resistance, metagenomics