阿奇霉素与人体肠道菌群体外相互作用的初步研究

Preliminary Study of Interaction between Azithromycin and Human Gut Microbiota in vitro

研究阿奇霉素对肠道菌群结构及其代谢产物的影响,为阿奇霉素的临床应用提供人体肠道菌群方面的理论依据。通过体外分批发酵、宏基因组测序及气相色谱等技术探讨阿奇霉素与人体肠道菌群的相互作用。结果表明,阿奇霉素暴露后与对照组相比,益生菌双歧杆菌属(Bifidobacterium)、片球菌属(Pediococcus)、拟杆菌属(Bacteroides)、小杆菌属(Dialister)、理研菌属(Petrimonas)和乳酸杆菌属(Lactobacillus)等的相对丰度显著降低,条件致病菌罗尔斯顿氏菌属(Ralstonia)和果胶杆菌属(Pectobacterium)的相对丰度显著提高(P<0.05);种水平上,长双歧杆菌(Bifidobacterium longum)、乳酸片球菌(Pediococcus acidilactici)、德氏乳杆菌(Lactobacillus delbrueckii)、Limosilactobacillus fermentum和链状双歧杆菌(Bifidobacterium catenulatum)等的相对丰度显著降低,小肠结肠炎耶尔森菌(Yersinia enterocolitica)和皮氏罗尔斯顿菌(Ralstonia pickettii)的相对丰度显著提高(P<0.05)。阿奇霉素还改变肠道菌群的新生霉素生物合成和核黄素代谢等途径及抗性基因的丰度,并降低乙酸含量,而肠道菌群对阿奇霉素的降解率较低。总之,阿奇霉素在体外发酵过程中影响人体肠道微生物群的细菌群落、代谢途径、耐药基因和乙酸含量。本文将为阿奇霉素与人体肠道菌群相互作用的研究提供参考。

To understand the effect of azithromycin on the human gut bacterial community and its metabolites,and provide a theoretical basis for the clinical application of azithromycin in human intestines,the interaction between azithromycin and human gut microbiota was studied using batch in vitro fermentation,metagenome sequencing,and gas chromatography.Results showed that azithromycin significantly reduced the relative abundance of Bifidobacterium,Pediococcus,Bacteroides,Dialister,Petrimonas,and Lactobacillus,and significantly increased the relative abundance of Ralstonia and Pectobacterium(P<0.05).At the species level,azithromycin significantly reduced the relative abundance of Bifidobacterium longum,Pediococcus acidilactici,Lactobacillus delbrueckii,Limosillactobacillus fermentum,and Bifidobacterium catenatum,while significantly increased the relative abundance of Yersinia enterocolitica and Ralstonia picettii(P<0.05).Azithromycin also changed the metabolic pathways and the abundance of resistance genes,such as novobiocin biosynthesis and riboflavin metabolism of gut microbiota,and reduced the content of acetic acid.However,the degradation rate of azithromycin by human gut microbiota is slight.In summary,azithromycin affects the bacterial community,metabolic pathway,drug resistance gene,and acetic acid content of human gut microbiota during in vitro fermentation.This paper provides reference for the study of the interaction between azithromycin and human gut microbiota.