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Different Dynamic Patterns of β-Lactams, Quinolones, Glycopeptides and Macrolides on Mouse Gut Microbial Diversity.

Yin J, M P, Wang S, Liao SX, Peng X, He Y, Chen YR, Shen HF, Su J, Chen Y, Jiang YX, Zhang GX, Zhou HW - PLoS ONE (2015)

Bottom Line: In general, the community changes induced by the three β-lactam antibiotics showed consistency in inhibiting Papillibacter, Prevotella and Alistipes while inducing massive growth of Clostridium.Vancomycin was unique in that it inhibited Firmicutes, mainly the genus Clostridium.Azithromycin and meropenem induced the growth of Enterococcus.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China 510515.

ABSTRACT
The adverse impact of antibiotics on the gut microbiota has attracted extensive interest, particularly due to the development of microbiome research techniques in recent years. However, a direct comparison of the dynamic effects of various types of antibiotics using the same animal model has not been available. In the present study, we selected six antibiotics from four categories with the broadest clinical usage, namely, β-lactams (Ceftriaxone Sodium, Cefoperazone/Sulbactam and meropenem), quinolones (ofloxacin), glycopeptides (vancomycin), and macrolides (azithromycin), to treat BALB/c mice. Stool samples were collected during and after the administration of antibiotics, and microbial diversity was analyzed through Illumina sequencing and bioinformatics analyses using QIIME. Both α and β diversity analyses showed that ceftriaxone sodium, cefoperazone/sulbactam, meropenem and vancomycin changed the gut microbiota dramatically by the second day of antibiotic administration whereas the influence of ofloxacin was trivial. Azithromycin clearly changed the gut microbiota but much less than vancomycin and the β-lactams. In general, the community changes induced by the three β-lactam antibiotics showed consistency in inhibiting Papillibacter, Prevotella and Alistipes while inducing massive growth of Clostridium. The low diversity and high Clostridium level might be an important cause of Clostridium difficile infection after usage of β-lactams. Vancomycin was unique in that it inhibited Firmicutes, mainly the genus Clostridium. On the other hand, it induced the growth of Escherichia and effect lasted for months afterward. Azithromycin and meropenem induced the growth of Enterococcus. These findings will be useful for understanding the potential adverse effects of antibiotics on the gut microbiome and ensuring their better usage.

No MeSH data available.


Related in: MedlinePlus

Microbial composition at the phylum level of distribution for different antibiotic groups.A.CK; B. CTR; C. OFL; D. CPZ; E. VAN; F. MEC; G AZI.I is sampling time before antibiotic treatment (I.1, I.2, I.3), II is the sampling during antibiotic administration (II.1, II.2, II.3, II.4), and III is after the antibiotic therapy (III.1, III.2, III.3, III.4, III.5, III.6, III.7, III.14, III.30, III.90). Here, 1, 2, 3, 4 and so on were sampling days.
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pone.0126712.g003: Microbial composition at the phylum level of distribution for different antibiotic groups.A.CK; B. CTR; C. OFL; D. CPZ; E. VAN; F. MEC; G AZI.I is sampling time before antibiotic treatment (I.1, I.2, I.3), II is the sampling during antibiotic administration (II.1, II.2, II.3, II.4), and III is after the antibiotic therapy (III.1, III.2, III.3, III.4, III.5, III.6, III.7, III.14, III.30, III.90). Here, 1, 2, 3, 4 and so on were sampling days.

Mentions: After Illumina sequencing of the16srRNA and standardizing the sequences obtained, we detected 28 phyla. More than 98.2% of the sequences belonged to Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria (Fig 3). At the early stage of the drug delivery period, Firmicutes was the largest phyla among the control and antibiotic groups. The control group was stable during the whole observation period. β-lactam antibiotics interfere with cell wall synthesis by binding to penicillin-binding proteins located in bacterial cell walls, which leads to suppression of peptidoglycan synthesis and finally to cell death [33]. During the whole drug delivery period, we observed Firmicutes increased and Bacteroidetes and Proteobacteria decreased in CTR and MEC (β-lactam group), with a return to normal after drug withdrawal. However, in CPZ, Firmicutes decreased and Proteobacteria increased during the drug delivery period, and Firmicutes increased early and decreased later after drug withdrawal. Previous studies by Henrik et al. [25, 31] and Panda et al. [32] showed results similar to the CPZ group, whereas the CTR and MEC results were not in agreement with their results. Quinolones inhibit bacterial DNA gyrase and topoisomerase IV in gram-negative and gram-positive groups, respectively [34]. In the OFL group, Firmicutes, Bacteroidetes and Actinobacteria did not change throughout the observation period, whereas Proteobacteria decreased after drug delivery and remained low until the end of observation. Similar results were obtained by Panda et al. [32] after quinolone treatment in the human gut. In the VAN group, Firmicutes decreased from the second day after drug delivery, and Proteobacteria was the dominant phylum until drug withdrawal. During the recovery period, Bacteroidetes first rose and then returned to normal. A previous study by Anne et al. [35] showed similar results in vancomycin-treated gut microbiota. Vancomycin has a unique mode of action, including inhibiting the second stage of cell wall synthesis of susceptible bacteria, altering the permeability of the cell membrane and selectively inhibiting ribonucleic acid synthesis [36]. The change in the AZI group is not significant. Macrolides inhibit protein synthesis in the bacterial cell by preventing peptidyl transferase activity, as well as by inhibiting ribosomal translocation [37].


Different Dynamic Patterns of β-Lactams, Quinolones, Glycopeptides and Macrolides on Mouse Gut Microbial Diversity.

Yin J, M P, Wang S, Liao SX, Peng X, He Y, Chen YR, Shen HF, Su J, Chen Y, Jiang YX, Zhang GX, Zhou HW - PLoS ONE (2015)

Microbial composition at the phylum level of distribution for different antibiotic groups.A.CK; B. CTR; C. OFL; D. CPZ; E. VAN; F. MEC; G AZI.I is sampling time before antibiotic treatment (I.1, I.2, I.3), II is the sampling during antibiotic administration (II.1, II.2, II.3, II.4), and III is after the antibiotic therapy (III.1, III.2, III.3, III.4, III.5, III.6, III.7, III.14, III.30, III.90). Here, 1, 2, 3, 4 and so on were sampling days.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4430517&req=5

pone.0126712.g003: Microbial composition at the phylum level of distribution for different antibiotic groups.A.CK; B. CTR; C. OFL; D. CPZ; E. VAN; F. MEC; G AZI.I is sampling time before antibiotic treatment (I.1, I.2, I.3), II is the sampling during antibiotic administration (II.1, II.2, II.3, II.4), and III is after the antibiotic therapy (III.1, III.2, III.3, III.4, III.5, III.6, III.7, III.14, III.30, III.90). Here, 1, 2, 3, 4 and so on were sampling days.
Mentions: After Illumina sequencing of the16srRNA and standardizing the sequences obtained, we detected 28 phyla. More than 98.2% of the sequences belonged to Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria (Fig 3). At the early stage of the drug delivery period, Firmicutes was the largest phyla among the control and antibiotic groups. The control group was stable during the whole observation period. β-lactam antibiotics interfere with cell wall synthesis by binding to penicillin-binding proteins located in bacterial cell walls, which leads to suppression of peptidoglycan synthesis and finally to cell death [33]. During the whole drug delivery period, we observed Firmicutes increased and Bacteroidetes and Proteobacteria decreased in CTR and MEC (β-lactam group), with a return to normal after drug withdrawal. However, in CPZ, Firmicutes decreased and Proteobacteria increased during the drug delivery period, and Firmicutes increased early and decreased later after drug withdrawal. Previous studies by Henrik et al. [25, 31] and Panda et al. [32] showed results similar to the CPZ group, whereas the CTR and MEC results were not in agreement with their results. Quinolones inhibit bacterial DNA gyrase and topoisomerase IV in gram-negative and gram-positive groups, respectively [34]. In the OFL group, Firmicutes, Bacteroidetes and Actinobacteria did not change throughout the observation period, whereas Proteobacteria decreased after drug delivery and remained low until the end of observation. Similar results were obtained by Panda et al. [32] after quinolone treatment in the human gut. In the VAN group, Firmicutes decreased from the second day after drug delivery, and Proteobacteria was the dominant phylum until drug withdrawal. During the recovery period, Bacteroidetes first rose and then returned to normal. A previous study by Anne et al. [35] showed similar results in vancomycin-treated gut microbiota. Vancomycin has a unique mode of action, including inhibiting the second stage of cell wall synthesis of susceptible bacteria, altering the permeability of the cell membrane and selectively inhibiting ribonucleic acid synthesis [36]. The change in the AZI group is not significant. Macrolides inhibit protein synthesis in the bacterial cell by preventing peptidyl transferase activity, as well as by inhibiting ribosomal translocation [37].

Bottom Line: In general, the community changes induced by the three β-lactam antibiotics showed consistency in inhibiting Papillibacter, Prevotella and Alistipes while inducing massive growth of Clostridium.Vancomycin was unique in that it inhibited Firmicutes, mainly the genus Clostridium.Azithromycin and meropenem induced the growth of Enterococcus.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China 510515.

ABSTRACT
The adverse impact of antibiotics on the gut microbiota has attracted extensive interest, particularly due to the development of microbiome research techniques in recent years. However, a direct comparison of the dynamic effects of various types of antibiotics using the same animal model has not been available. In the present study, we selected six antibiotics from four categories with the broadest clinical usage, namely, β-lactams (Ceftriaxone Sodium, Cefoperazone/Sulbactam and meropenem), quinolones (ofloxacin), glycopeptides (vancomycin), and macrolides (azithromycin), to treat BALB/c mice. Stool samples were collected during and after the administration of antibiotics, and microbial diversity was analyzed through Illumina sequencing and bioinformatics analyses using QIIME. Both α and β diversity analyses showed that ceftriaxone sodium, cefoperazone/sulbactam, meropenem and vancomycin changed the gut microbiota dramatically by the second day of antibiotic administration whereas the influence of ofloxacin was trivial. Azithromycin clearly changed the gut microbiota but much less than vancomycin and the β-lactams. In general, the community changes induced by the three β-lactam antibiotics showed consistency in inhibiting Papillibacter, Prevotella and Alistipes while inducing massive growth of Clostridium. The low diversity and high Clostridium level might be an important cause of Clostridium difficile infection after usage of β-lactams. Vancomycin was unique in that it inhibited Firmicutes, mainly the genus Clostridium. On the other hand, it induced the growth of Escherichia and effect lasted for months afterward. Azithromycin and meropenem induced the growth of Enterococcus. These findings will be useful for understanding the potential adverse effects of antibiotics on the gut microbiome and ensuring their better usage.

No MeSH data available.


Related in: MedlinePlus