摘要
【目的】探究抗抑郁药米氮平在复杂肠道环境中对微生物耐药组的影响。【方法】基于粪便和盲肠内容物的宏基因组测序数据,通过reads比对和宏基因组组装分析耐药基因及宿主情况。【结果】共鉴定出29类耐药基因(antibiotic resistance gene,ARG),包含610种亚型。杆菌肽、四环素和万古霉素类为主要ARG类型。慢性约束应激(chronic restrain stress,CRS)处理增加了ARG总丰度,显著提高了氨基糖苷类、大环内酯-林可酰胺-链阳菌素类(macrolide-lincosamidestreptogramin,MLS)类及四环素类高风险ARG(tetM、tetO、tet40)的丰度。口服米氮平对耐药组的影响具有初始菌群依赖性:它增加健康大鼠肠道ARG总丰度,降低抑郁大鼠肠道ARG总丰度。米氮平还显著增加了健康大鼠肠道万古霉素类、氨基糖苷类和莫匹罗星类ARG,以及抑郁大鼠肠道四环素耐药基因tetP、多重耐药基因ompR等的丰度。芽孢杆菌门、拟杆菌门和假单胞菌门是肠道优势菌门,同时也是主要ARG细菌宿主。芽孢杆菌门作为氨基糖苷类和MLS类耐药基因的主要宿主菌门,CRS处理后该菌门丰度的增加是导致这2类ARG显著富集的重要原因。CRS还增加了耐万古霉素肠球菌等致病菌的比例。乳杆菌属(Lactobacillus)和经黏液真杆菌属(Blautia)分别被鉴定为tetP和ompR的潜在宿主。口服米氮平后抑郁大鼠肠道Lactobacillus和Blautia丰度的显著增加是tetP和ompR显著富集的重要原因。【结论】CRS处理通过增加高风险ARG丰度及携带ARG的致病菌比例从而增加肠道耐药风险,口服米氮平对肠道微生物耐药组的影响具有初始菌群依赖性。本研究为深入理解非抗生素药物与肠道耐药性的关系提供了依据,对防控抗生素耐药性传播具有重要意义。
[Objective]To investigate the effects of the antidepressant mirtazapine on the microbial resistome in complex intestinal environments.[Methods]We employed read mapping and metagenomic assembly to analyze the antibiotic resistance genes(ARGs)and their bacterial hosts based on metagenomic sequencing data of fecal and cecal content samples.[Results]A total of 29 classes of ARGs,comprising 610 subtypes,were identified.Bacitracin-,tetracycline-,and vancomycin-class ARGs were the predominant types.Chronic restrain stress(CRS)increased the total abundance of ARGs,significantly elevating the abundance of high-risk ARGs belonging to aminoglycoside,MLS(macrolide-lincosamide-streptogramin),and tetracycline classes(e.g.,tetM,tetO,and tet40).Oral administration of mirtazapine exhibited initial microbiota-dependent effects on the resistome.It increased the total abundance of ARGs in healthy rats but decreased that in depressed rats.In addition,mirtazapine significantly enhanced the abundance of vancomycin-,aminoglycoside-,and mupirocin-class ARGs in healthy rats,as well as the tetracycline resistance gene tetP and multidrug resistance gene ompR in depressed rats.Bacillota,Bacteroidota,and Pseudomonadota were the dominant phyla of gut microbiota and served as the primary bacterial hosts of ARGs.Bacillota,as the main host phylum for aminoglycoside and MLS-class ARGs,showed increased abundance after CRS treatment,which was a key factor driving the significant enrichment of these two ARG classes.Furthermore,CRS increased the proportion of pathogenic bacteria such as vancomycin-resistant enterococci.Lactobacillus and Blautia were identified as potential hosts of tetP and ompR,respectively.The significant increases in the abundance of Lactobacillus and Blautia in the intestines of depressed rats after oral mirtazapine administration were critical factors for the marked enrichment of tetP and ompR.[Conclusion]CRS increases gut microbiota resistance risks by elevating the abundance of high-risk ARGs and pathogenic bacteria carrying ARGs.The effects of oral mirtazapine on the gut resistome are dependent on the initial microbiota composition.This study provides insights into the relationship between non-antibiotic drugs and gut microbiota resistance,offering important implications for the prevention and control of antibiotic resistance transmission.
作者
陈亚琳
闫鹤
CHEN Yalin;YAN He(School of Food Science and Engineering,South China University of Technology,Guangzhou,Guangdong,China)
出处
《微生物学报》
北大核心
2025年第12期5500-5523,共24页
Acta Microbiologica Sinica
基金
国家自然科学基金(32170064)。
关键词
米氮平
肠道菌群
抗生素耐药性
细菌宿主
mirtazapine
gut microbiota
antibiotic resistance
bacterial hosts
