Table 4.
Associations between antibiotic use and changes in taxonomic composition of the microbiome in children up to 12 years
Study Author, year, type of study, country, duration. |
Antibiotic (days of treatment where given) |
Time from exposure to analysis | Actinobacteria (includes genus Bifidobacteria) |
Bacteroidetes | Firmicutes (gram positive) |
Proteobacteria (gram negative) |
---|---|---|---|---|---|---|
Bai et al.32 Cross-Sectional China 1–12 years |
Cephalosporin, Penicillin 10 days |
1–4 weeks | No change in Actinobacteria | F/B ratio decreased by approx. 1/3(p < .05) * (increase in Bacteroidetes) |
F/B ratio decreased by approx. 1/3 (p < .05) * (decrease in Firmicutes) |
No change |
Bokulich et al.33 Cohort USA 0–2 years |
Cephalosporin Beta lactams Macrolides Quinolones Nitrofurantoin |
3–139 days | No change in Bifidobacteria | Increased (p < .05) * | Clostridiales decreased from 3–9 months of age* | Increased (p < .05) * |
Brunser et al.34 Cohort Chile 0–2 years |
Amoxicillin 7 days |
1–3 weeks | No change in Bifidobacteria | No change | n/a |
E. coli increased vs baseline (Log 4.77 ± 0.96 vs Log 5.10 ± 1.39 p = .015) |
Fouhy et al.36 Cohort Ireland Neonates |
Ampicillin; gentamicin 2–9 days |
4 weeks | Lower levels of Bifidobacteria at 4 weeks vs control (5% vs 25%; p = .013); no difference at 8 weeks |
No change | Lower levels of Lactobacillus at 4 weeks vs control (1% vs 4%; p < .009); no difference at 8 weeks |
Higher proportions of Proteobacteria (44% vs 23%; p < .005) and Enterobacteriaceae (50% vs 32%; p = .006) at 8 weeks vs control |
Korpela et al.37 Retrospective cohort Finland 2–7 years |
Macrolides (M) Penicillins (P) |
<6 months | Exposure in previous 6 months M: Bifidobacterium (0.23-fold decrease p < .004) P: Bifidobacterium: no change |
Exposure in previous 6 months M: Bacteroides increased (2.04-fold change p < .004) P: Bacteroides: no change |
Exposure in previous 6 months M: Lactobacillus decreased (0.12-fold change p < .004), Clostridium increased (2.68-fold change p < .004) P: Lactobacillus decreased (0.11-fold change p < .004), Clostridium: no change |
M: Proteobacteria increased (1.96-fold change p < .02) with exposure in previous 6 months P: no change |
Mangin et al.38 Cohort Chile 6–59 months |
Amoxicillin 7 days |
0 days | Total Bifidobacterium concentrations not significantly altered but complete disappearance of Bifidobacterium adolescentis species (0% vs 36.4% (p < .001) |
n/a | n/a | n/a |
Parker et al.40 RCT India 6–11 months |
Azithromycin 3 days |
12 days | No change in Actinobacteria or Bifidobacterium | No change | No change | Proteobacteria reduced (relative abundance mean % ± SD: 15.889 ±13.207 (placebo) vs 10.200± 15.401 (azithromycin), FDR p < .001) E.coli reduced (relative abundance mean % ± SD:12.087± 12.457 (placebo) vs 7.309 ±13.258 (azithromycin), FDR p < .013) |
Penders et al.41 Cross sectional Netherlands 1 month |
Amoxicillin** | < 1 month | Bifidobacteria median count placebo log10 CFU/g feces 10.70 vs amoxicillin log CFU/g feces 10.29 (p < .01) | Bacteroides fragilis median count placebo log10 CFU/g feces 9.31 vs amoxicillin log10 CFU/g 6.39 (P < .01) | No change (lactobacilli) | No change in Clostridium difficile and E.Coli |
Wei et al.29 RCT Denmark 1–3 years |
Azithromycin 3 days |
14 days | 50 x reduction (fold change) in genus Bifidobacterium at 14 days (p adjusted < 0.011 (FDR p < .05) | n/a | n/a | n/a |
Yassour et al.42 Cohort Finland 2–36 months |
Amoxicillin Cefalexin Clarithromycin Amoxicillin and clavulanic acid Trimethoprim and sulfadiazine Azithromycin Cefaclor Penicillin G Netilmicin |
< 1 month | n/a | n/a | Decrease in abundance of species from clostridium clusters and 14XIVa IV (T regulatory immune cells) at aged 3 (median abundance ~9% vs ~15% control) b (p = .037) | n/a |
Key: †Confidence intervals or Standard Deviation not available. # Approximate value taken from bar chart. No confidence intervals or SD available. *no raw data. ** authors state that the antibiotics taken were ‘mainly amoxicillin’. b raw data not given; approximate values taken from graph.
Abbreviations: CFU/g = Colony forming unit/gram; F/B ratio = Firmicutes/Bacteroidetes ratio. FDR – false discovery rate correction. M = macrolides . P = penicillins. n/a = Data not available.