盐酸安非他酮对SD大鼠肠道菌群耐药组的影响

doi:10.12141/j.issn.1000-565X.240258

摘要/Abstract

摘要：

为探究抗抑郁药盐酸安非他酮对肠道菌群耐药组的影响，选用SD大鼠为研究对象，分别采用16S rRNA扩增子及宏基因组测序技术，分析盐酸安非他酮对大鼠粪便和盲肠内容物菌群及其耐药组的影响，并挖掘之间的关联。结果表明：粪便和盲肠内容物样本中主要抗生素耐药基因（ARGs）类型包括杆菌肽类、四环素、万古霉素及大环内酯-林可酰胺-链菌素类（MLS）等。与对照组（HC）相比，盐酸安非他酮灌胃干预组（Bup-PO）提高了大鼠粪便和盲肠内容物样本中细菌ARG总丰度，但仅在粪便样本中达到显著性差异。在ARG类型上，相比于HC组，Bup-PO组显著提高了粪便样本中氨基糖苷类、杆菌肽类、莫匹罗星、利福霉素类、四环素、万古霉素6类耐药基因类型的相对丰度，且增加了万古霉素抗性基因的种类。在盲肠内容物样本中，Bup-PO组显著提高了四环素、柔红霉素和磷霉素3类耐药基因类型的相对丰度。在ARG亚型上，在粪便样中，相比于HC组，Bup-PO组显著提高了万古霉素（vanAG、vanRI、vanSA、vanSI），四环素（tetM、tetO、tet32），杆菌肽类（bceA、bcrA）和利福霉素类（ rpoB）耐药基因的相对丰度。在盲肠内容物样本中，灌胃盐酸安非他酮给药对ARGs的影响与粪便样本中有所不同，表现为降低了大环内酯-林可酰胺-链菌素类（lmrB）耐药基因的相对丰度，但提高了另一种大环内酯-林可酰胺-链菌素类（macB）耐药基因的相对丰度丰度。同时，灌胃给药盐酸安非他酮还提高了四环素（tetW）和柔红霉素（drrA）耐药基因的相对丰度。以上结果表明，盐酸安非他酮干预有增加大鼠肠道菌群抗生素耐药性的风险。UCG-005和norank_ f__norank_o__Clostridia_UCG-014是大鼠粪便和盲肠内容物菌群的主要细菌属，相关性分析结果表明，UCG-005可能是四环素、利福霉素类、莫匹罗星、杆菌肽类、万古霉素耐药基因的潜在细菌宿主，而norank_ f__norank_o__Clostridia_UCG-014可能是柔红霉素耐药基因的细菌宿主，它们在盐酸安非他酮给药后增加可能是导致这6种类型耐药基因丰度增加的原因。

关键词: 抗抑郁药, 盐酸安非他酮, 肠道菌群, 抗生素耐药性, 宏基因组学

Abstract:

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.

Key words: antidepressant, bupropin hydrochloride, gut microbiota, antibiotic resistance, metagenomics

中图分类号:

R971

闫鹤, 陈春霞, 刘宗保, 李佳林, 詹诗皿. 盐酸安非他酮对SD大鼠肠道菌群耐药组的影响[J]. 华南理工大学学报(自然科学版), 2025, 53(10): 155-173.

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 Edition), 2025, 53(10): 155-173.

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粪便样本	Bup-PO.uniq	HC.uniq
万古霉素	vanAo2	vanYPt2
	vanI	vanSO
	vanO
	vanRB
	vanRE
	vanRM
	vanSM
	vanT-Cd
	vanTE
	vanX
	vanXA
	vanXI
	vanXO
	vanXPt
	vanYA
	vanYM

盲肠内容物样本	Bup-PO.uniq	HC.uniq
万古霉素	vanHO	vanZ1
	vanHA	vanXO
	vanTN	vanXPt
	vanRM	vanI
	vanRB	vanSN
	vanHAo1