Background
Vancomycin is one of the potent antibiotics to perturb the gut microbiota [1]. Vancomycin treatment caused a significant alteration in the composition and diversity of the commensal gut microbiota of the host[2].Vancomycin specifically blocks peptide cross-linking in the bacterial peptidoglycan by recognizing terminal peptide sequences and blocking their binding site to enzymatic cross-linkers. Vancomycin has previously been shown to be active against B. burgdorferi in vitro[5,6].
Low to moderate doses of vancomycin ( 2.0 μg/mL for 24 h) produced small alterations in cell shape and that as the dose was increased, cell speed decreased. Vancomycin concentrations >1.0 μg/mL also inhibited cell growth and led to bleb formation on a fraction of the cells[3]. The addition of vancomycin at a concentration of 10ug/ml-1 to the wash solution of the cell-saver achieved similar concentrations in the autologous blood concentrate recovered allowing for bacterial removal, with negative blood cultures in all cases[4].
Metagenomic analysis of gut microbiota revealed that the treatment with vancomycin caused a significant decrease in the relative abundance of Firmicutes and Bacteroidetes phyla with a time-dependent increase in Proteobacteria and Verrucomicrobia phyla. Maximum restoration (> 70%) of gut microbiota happened by the 15th day of withdrawal of vancomycin. BALB/c mice showed a more efficient restoration of gut microbiota compared to C57BL/6 mice[7]. Mice treated with vancomycin alone had a better clinical outcome in the treatment phase of CDI than mice treated with metronidazole alone[8].
参考文献:
[1]. Carding S, Verbeke K, et,al.Dysbiosis of the gut microbiota in disease. Microb Ecol Health Dis. 2015 Feb 2;26:26191. doi: 10.3402/mehd.v26.26191. PMID: 25651997; PMCID: PMC4315779.
[2]. Vrieze A, Out C, et,al. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. J Hepatol. 2014 Apr;60(4):824-31. doi: 10.1016/j.jhep.2013.11.034. Epub 2013 Dec 6. PMID: 24316517
[3]. Harman MW, Hamby AE, et,al. Vancomycin Reduces Cell Wall Stiffness and Slows Swim Speed of the Lyme Disease Bacterium. Biophys J. 2017 Feb 28;112(4):746-754. doi: 10.1016/j.bpj.2016.12.039. PMID: 28256234; PMCID: PMC5340155.
[4]. Perez-Ferrer A, Gredilla-Díaz E, et,al. Vancomycin added to the wash solution of the cell-saver. Effect on bacterial contamination. Rev Esp Anestesiol Reanim. 2017 Apr;64(4):185-191. English, Spanish. doi: 10.1016/j.redar.2016.10.002. Epub 2017 Jan 13. PMID: 28094033.
[5]. Dever LL, Jorgensen JH, et,al. In vitro activity of vancomycin against the spirochete Borrelia burgdorferi. Antimicrob Agents Chemother. 1993 May;37(5):1115-21. doi: 10.1128/AAC.37.5.1115. PMID: 8517700; PMCID: PMC187913
[6]. Hunfeld KP, Weigand J, et,al.In vitro activity of mezlocillin, meropenem, aztreonam, vancomycin, teicoplanin, ribostamycin and fusidic acid against Borrelia burgdorferi. Int J Antimicrob Agents. 2001 Mar;17(3):203-8. doi: 10.1016/s0924-8579(00)00342-3. PMID: 11282265.
[7]. Ray P, Pandey U, et,al.Vancomycin-Induced Changes in Host Immunity and Behavior: Comparative Genomic and Metagenomic Analysis in C57BL/6 and BALB/c Mice. Dig Dis Sci. 2021 Nov;66(11):3776-3791. doi: 10.1007/s10620-020-06729-x. Epub 2021 Jan 1. PMID: 33386517.
[8]. Erikstrup LT, Aarup M, et,al.Treatment of Clostridium difficile infection in mice with vancomycin alone is as effective as treatment with vancomycin and metronidazole in combination. BMJ Open Gastroenterol. 2015 Nov 2;2(1):e000038. doi: 10.1136/bmjgast-2015-000038. PMID: 26568840; PMCID: PMC4641438.
万古霉素是扰乱肠道微生物群的强效抗生素之一[1]。万古霉素处理引起宿主肠道共生菌群组成和多样性的显着改变[2]。万古霉素通过识别末端肽序列并阻断它们的结合，特异性阻断细菌肽聚糖中的肽交联酶促交联剂的位点。万古霉素先前已被证明在体外对伯氏疏螺旋体具有活性[5,6]。
低至中等剂量的万古霉素（2.0 μg/mL，持续 24 小时）使细胞形状发生微小变化，并且随着剂量增加，细胞速度降低。万古霉素浓度 >1.0 μg/mL 也抑制细胞生长并导致部分细胞形成气泡[3]。将浓度为 10ug/ml-1 的万古霉素添加到细胞保护剂的洗涤液中，在回收的自体血液浓缩液中达到相似的浓度，允许去除细菌，所有情况下血培养均为阴性[4].
肠道微生物群的宏基因组分析显示，万古霉素治疗导致厚壁菌门和拟杆菌门的相对丰度显着降低，而变形菌门和疣微菌门的相对丰度随时间增加。肠道微生物群的最大恢复 (> 70%) 发生在停用万古霉素的第 15 天。与 C57BL/6 小鼠相比，BALB/c 小鼠肠道菌群恢复更有效[7]。单独使用万古霉素治疗的小鼠在 CDI 治疗阶段的临床结果优于单独使用甲硝唑治疗的小鼠[8]。
Protocol
| Cell experiment [1]: |
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Cell lines
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B. burgdorferi
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Preparation Method
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Vancomycin was added at a final concentration of 0.5 -2.0 μg/mL into exponentially growing Borrelia spirochetes and incubated for up to 48 h.
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Reaction Conditions
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0.5-2.0 μg/mL Vancomycinfor 48 h
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Applications
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Low to moderate doses of vancomycin ( 2.0 μg/mL for 24 h) produced small alterations in cell shape and that as the dose was increased, cell speed decreased. Vancomycin concentrations >1.0 μg/mL also inhibited cell growth and led to bleb formation on a fraction of the cells.
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| Animal experiment [2]: |
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Animal models
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C57BL/6 (Th1) and BALB/c (Th2) of 6-8 weeks
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Preparation Method
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Both Th1 (C57BL/6)- and Th2 (BALB/c)-biased mice were treated with vancomycin (at 50 mg per kg of body weight) for six consecutive days. 0.5 ml of vancomycin was orally gavaged twice daily at a gap of 12 h. Following the withdrawal of 6 days of treatment with vancomycin, mice were observed for 60 days.
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Dosage form
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50 mg/kg twice daily at a gap of 12 h,oral
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Applications
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The gut microbiome profiling, behavior, and immune responses varied significantly between Th1- and Th2-biased mice. By withdrawing the treatment with vancomycin of major gut microbes, important physiological and behavioral changes of both mice strains returned to the normal (untreated control) level.
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参考文献:
[1]. Harman MW, Hamby AE, et,al. Vancomycin Reduces Cell Wall Stiffness and Slows Swim Speed of the Lyme Disease Bacterium. Biophys J. 2017 Feb 28;112(4):746-754. doi: 10.1016/j.bpj.2016.12.039. PMID: 28256234; PMCID: PMC5340155.
[2]. Ray P, Pandey U, et,al. Vancomycin-Induced Changes in Host Immunity and Behavior: Comparative Genomic and Metagenomic Analysis in C57BL/6 and BALB/c Mice. Dig Dis Sci. 2021 Nov;66(11):3776-3791. doi: 10.1007/s10620-020-06729-x. Epub 2021 Jan 1. PMID: 33386517.
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