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
-
摘要: 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。Abstract: 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.
-
-
Wang J Y, Xiong K, Zhao S L, et al. Long-term effects of multi-drug-resistant tuberculosis treatment on gut microbiota and its health consequences[J]. Frontiers in Microbiology, 2020, 11:53 Mulder M, Radjabzadeh D, Kiefte-de Jong J C, et al. Long-term effects of antimicrobial drugs on the composition of the human gut microbiota[J]. Gut Microbes, 2020, 12(1):1795492 Olekhnovich E I, Manolov A I, Samoilov A E, et al. Shifts in the human gut microbiota structure caused by quadruple Helicobacter pylori eradication therapy[J]. Frontiers in Microbiology, 2019, 10:1902 Elvers K T, Wilson V J, Hammond A, et al. Antibiotic-induced changes in the human gut microbiota for the most commonly prescribed antibiotics in primary care in the UK:A systematic review[J]. BMJ Open, 2020, 10(9):e035677 McDonnell L, Gilkes A, Ashworth M, et al. Association between antibiotics and gut microbiome dysbiosis in children:Systematic review and meta-analysis[J]. Gut Microbes, 2021, 13(1):1-18 Kobayashi T, Tsuyuguchi K, Yoshida S, et al. Resumption/efficacy and safety of an azithromycin-containing regimen against Mycobacterium avium complex lung disease in patients who experienced adverse effects with a clarithromycin-containing regimen[J]. Respiratory Investigation, 2021, 59(2):212-217 Kwon Y S, Han M, Kwon B S, et al. Discontinuation rates attributed to adverse events and treatment outcomes between clarithromycin and azithromycin in Mycobacterium avium complex lung disease:A propensity score analysis[J]. Journal of Global Antimicrobial Resistance, 2020, 22:106-112 Llorens E, Ginebreda A, la Farré M, et al. Occurrence of regulated pollutants in populated Mediterranean Basins:Ecotoxicological risk and effects on biological quality[J]. The Science of the Total Environment, 2020, 747:141224 Oldenburg C E, Sié A L, Coulibaly B, et al. Effect of commonly used pediatric antibiotics on gut microbial diversity in preschool children in Burkina Faso:A randomized clinical trial[J]. Open Forum Infectious Diseases, 2018, 5(11):ofy289 Vallet N, Le Grand S, Bondeelle L, et al. Azithromycin promotes relapse by disrupting immune and metabolic networks after allogeneic stem cell transplantation[J]. Blood, 2022, 140(23):2500-2513 Yu J, Chen X, Zhang Y J, et al. Antibiotic Azithromycin inhibits brown/beige fat functionality and promotes obesity in human and rodents[J]. Theranostics, 2022, 12(3):1187-1203 Doan T, Hinterwirth A, Worden L, et al. Gut microbiome alteration in MORDOR I:A community-randomized trial of mass azithromycin distribution[J]. Nature Medicine, 2019, 25(9):1370-1376 Yang X M, Liu X X, Yang C, et al. A conjugative IncI1 plasmid carrying erm(B) and blaCTX-M-104 that mediates resistance to azithromycin and cephalosporins[J]. Microbiology Spectrum, 2021, 9(2):e0028621 Klancic T, Laforest-Lapointe I, Wong J, et al. Concurrent prebiotic intake reverses insulin resistance induced by early-life pulsed antibiotic in rats[J]. Biomedicines, 2021, 9(1):66 Tang Q, Li S Q, Fang C J, et al. Evaluating the reparative effects and the mechanism of action of docosahexaenoic acid on azithromycin-induced lipid metabolism dysfunction[J]. Food and Chemical Toxicology:An International Journal Published for the British Industrial Biological Research Association, 2022, 159:112699 Nikolaou E, Kamilari E, Savkov D, et al. Intestinal microbiome analysis demonstrates azithromycin post-treatment effects improve when combined with lactulose[J]. World Journal of Pediatrics, 2020, 16(2):168-176 Raju S C, Viljakainen H, Figueiredo R A O, et al. Antimicrobial drug use in the first decade of life influences saliva microbiota diversity and composition[J]. Microbiome, 2020, 8(1):121 Zhao C H, Hu Y F, Chen H H, et al. An in vitro evaluation of the effects of different statins on the structure and function of human gut bacterial community[J]. PLoS One, 2020, 15(3):e0230200 Guler S A, Clarenbach C, Brutsche M, et al. Azithromycin for the treatment of chronic cough in idiopathic pulmonary fibrosis:A randomized controlled crossover trial[J]. Annals of the American Thoracic Society, 2021, 18(12):2018-2026 Luke D R, Foulds G. Disposition of oral azithromycin in humans[J]. Clinical Pharmacology and Therapeutics, 1997, 61(6):641-648 Maier L S, Pruteanu M, Kuhn M, et al. Extensive impact of non-antibiotic drugs on human gut bacteria[J]. Nature, 2018, 555(7698):623-628 Rousta E, Oka A, Liu B, et al. The emulsifier carboxymethylcellulose induces more aggressive colitis in humanized mice with inflammatory bowel disease microbiota than polysorbate-80[J]. Nutrients, 2021, 13(10):3565 胡芳, 刘莉, 孟卫. 分光光度法测定阿奇霉素的改进[J]. 光谱实验室, 2011, 28(3):1499-1502 Hu F, Liu L, Meng W. Determination of azithromycin by modified spectrophotometry[J]. Chinese Journal of Spectroscopy Laboratory, 2011, 28(3):1499-1502(in Chinese)
赵昌会, 陈华海, 胡云霏, 等. 氯霉素对体外模拟人体肠道菌群的影响[J]. 应用与环境生物学报, 2023, 29(4):1-10 Zhao C H, Chen H H, Hu Y F, et al. Effect of chloramphenicol on simulated human intestinal microbiota in vitro[J]. Chinese Journal of Applied and Environmental Biology, 2023, 29(4):1-10(in Chinese)
Parker E P K, Praharaj I, John J, et al. Changes in the intestinal microbiota following the administration of azithromycin in a randomised placebo-controlled trial among infants in South India[J]. Scientific Reports, 2017, 7(1):9168 Li R, Wang H X, Shi Q F, et al. Effects of oral florfenicol and azithromycin on gut microbiota and adipogenesis in mice[J]. PLoS One, 2017, 12(7):e0181690 Chaima D, Pickering H, Hart J D, et al. Biannual administrations of azithromycin and the gastrointestinal microbiome of Malawian children:A nested cohort study within a randomized controlled trial[J]. Frontiers in Public Health, 2022, 10:756318 Yin J, Prabhakar M, Wang S, et al. Different dynamic patterns of β-lactams, quinolones, glycopeptides and macrolides on mouse gut microbial diversity[J]. PLoS One, 2015, 10(5):e0126712 Ren X H, Xu J, Zhang Y Y, et al. Bacterial alterations in post-cholecystectomy patients are associated with colorectal cancer[J]. Frontiers in Oncology, 2020, 10:1418 Chung The H, Nguyen Ngoc Minh C, Tran Thi Hong C, et al. Exploring the genomic diversity and antimicrobial susceptibility of Bifidobacterium pseudocatenulatum in a Vietnamese population[J]. Microbiology Spectrum, 2021, 9(2):e0052621 Ayerbe L, Risco-Risco C, Forgnone I, et al. Azithromycin in patients with COVID-19:A systematic review and meta-analysis[J]. The Journal of Antimicrobial Chemotherapy, 2022, 77(2):303-309 Hazan S. Microbiome-based hypothesis on ivermectin's mechanism in COVID-19:Ivermectin feeds bifidobacteria to boost immunity[J]. Frontiers in Microbiology, 2022, 13:952321 Fan S N, Zhang K, Zhang J H, et al. Analysis of the effect of phototherapy on intestinal probiotics and metabolism in newborns with jaundice[J]. Frontiers in Pediatrics, 2022, 10:878473 Li X Y, Feng R, Zhou P, et al. Construction and characterization of Juglans regia L. polyphenols nanoparticles based on bovine serum albumin and Hohenbuehelia serotina polysaccharides, and their gastrointestinal digestion and colonic fermentation in vitro[J]. Food & Function, 2021, 12(21):10397-10410 Wang H H, Zhang K B, Wu L, et al. Prediction of pathogenic factors in dysbiotic gut microbiomes of colorectal cancer patients using reverse microbiomics[J]. Frontiers in Oncology, 2022, 12:882874 Xi Y, Liu F, Qiu B, et al. Analysis of gut microbiota signature and microbe-disease progression associations in locally advanced non-small cell lung cancer patients treated with concurrent chemoradiotherapy[J]. Frontiers in Cellular and Infection Microbiology, 2022, 12:892401 Huang R, He K, Duan X P, et al. Changes of intestinal microflora in colorectal cancer patients after surgical resection and chemotherapy[J]. Computational and Mathematical Methods in Medicine, 2022, 2022:1940846 Yang X, Tang T, Wen J, et al. Effects of S24-7 on the weight of progeny rats after exposure to ceftriaxone sodium during pregnancy[J]. BMC Microbiology, 2021, 21(1):166 Wen M, Liu T H, Zhao M Y, et al. Correlation analysis between gut microbiota and metabolites in children with systemic lupus erythematosus[J]. Journal of Immunology Research, 2021, 2021:5579608 Chen G L, Zhang Y, Wang W Y, et al. Partners of patients with ulcerative colitis exhibit a biologically relevant dysbiosis in fecal microbial metacommunities[J]. World Journal of Gastroenterology, 2017, 23(25):4624-4631 Kim S W, Van Kessel J A S, Haley B J. Genome sequences of antibiotic-resistant Escherichia coli isolated from veal calves in the USA[J]. Journal of Global Antimicrobial Resistance, 2021, 26:69-73 Serafini F, Bottacini F, Viappiani A, et al. Insights into physiological and genetic mupirocin susceptibility in bifidobacteria[J]. Applied and Environmental Microbiology, 2011, 77(9):3141-3146 Tóth A G, Csabai I, Maróti G, et al. A glimpse of antimicrobial resistance gene diversity in kefir and yoghurt[J]. Scientific Reports, 2020, 10:22458 Zhang X, Zhao H X, Du J, et al. Occurrence, removal, and risk assessment of antibiotics in 12 wastewater treatment plants from Dalian, China[J]. Environmental Science and Pollution Research International, 2017, 24(19):16478-16487 -
点击查看大图
计量
- 文章访问数: 1956
- HTML全文浏览数: 1956
- PDF下载数: 158
- 施引文献: 0
下载:
