Table 1.
The main characteristics of the included studies
| Study | Country | Study design a | Population | Antibiotic (and additional) treatment | Probiotic supplementation | Microbiome analysis method | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Number of randomized patients (female %) | Age (years - mean ± SD) in the intervention (and control) groups | Indication | Type and dose | Duration (days) | Type and dose | Duration (days) | ||||
| Cárdenas et al. (2020) [55] | Ecuador | single-blinded RCT | 38 (60.5) |
37.9 ± 7.2 (39.5 ± 10.7) |
Helicobacter pylori infection |
Amoxicillin 1 g tid, tinidazole 1 g qid, omeprazole 40 mg bid | 14 |
Saccharomyces boulardii CNCM I-745 22.5 × 109 CFU/day |
14 | 16S rRNA sequencing |
| Chen et al. (2018) [56] | China | open-label RCT | 70 (78.5) |
43.89 ± 12.50 (43.20 ± 12.45) |
Helicobacter pylori infection |
Pantoprazole 40 mg, amoxicillin 1000 mg, furazolidone 100 mg, colloidal bismuth pectin 0.4 g, bid | 14 |
Clostridium butyricum 3 × 40 mg/day |
14 | 16S rRNA sequencing |
| De Wolfe et al. (2018) [53] | USA | double-blinded, placebo controlled RCT | 31 (N.D.) |
N.D. (N.D.) |
Clostridioides difficile infection | Standard of care antibiotics (vancomycin, metronidazole, or fidaxomicin) | 28 |
Lactobacillus acidophilus NCFM® (ATCC 700396), Lactobacillus paracasei Lpc-37 (ATCC SD5275), Bifidobacterium lactis Bi-07 (ATCC SC5220), and Bifidobacterium lactis Bl-04 (ATCC SD5219). 1.7 × 1010 CFU/day |
28 | 16S rRNA sequencing |
| Kabbani et al. (2017) [61] | USA | open-label RCT | 24 (59) |
N.D. (N.D.) |
Healthy volunteers no indication |
Amoxicillin-clavulanate 875/125 mg, bid | 7 |
Saccharomyces boulardii (SB) CNCM I-745 (syn. CBS 5926) 2 × 500 mg/day |
14 | 16S rRNA gene pyrosequencing (bTEFAP). |
| Kakiuchi et al. (2020) [50] | Japan | open-label RCT | 65 (44.6) |
15.31 ± 0.32 (15.08 ± 0.28) |
Helicobacter pylori infection |
Vonoprazan 20 mg, amoxicillin 750 mg, clarithromycin 400 mg bid | 7 |
Enterococcus faecium 129 BIO 3B-R. 3 tablets/day |
7 | 16S rDNA sequencing |
| MacPherson et al. (2018) [51] | Canada | double-blinded, placebo-controlled RCT | 70 (N.D.) |
N.D. (N.D.) |
Healthy volunteers no indication |
Amoxicillin trihydrate 875 mg, potassium clavulanate 125 mg | 7 |
Lactobacillus rhamnosus R0011 and Lactobacillus helveticus R0052 3.8 × 109 CFU and 0.2 × 109 CFU/day |
14 | 16S rRNA gene amplicon, shotgun metagenomics sequencing |
| Oh et al. (2016) [43] | Korea | RCT | 20 (30) |
51.7 ± 0.79 (49.3 ± 3.56) |
Helicobacter pylori infection |
Clarithromycin 500 mg, amoxicillin 1000 mg, lansoprazole 30 mg bid | 14 |
Streptococcus faecium and Bacillus subtilis 2 × (9 × 108 and 1 × 108)/day |
14 | 16S rRNA gene-pyrosequencing |
| Tang et al. (2021) [52] | China | placebo-controlled, multi-center RCT | 151 (34.4) |
43.29 ± 11.30 (45.32 ± 10.98) |
Helicobacter pylori infection |
Esomeprazole 20 mg, amoxicillin 1000 mg furazolidone 100 mg, bismuth potassium citrate 220 mg bid | 14 |
Enterococcus faecium and Bacillus subtilis 3 × (4.5 × 108 and 5.0 × 107) CFU/day |
28 | 16S rRNA high-throughput sequencing |
| Zhong et al. (2021) [54] | China | open-label parallel RCT | 42 (52.4) |
all neonates (all neonates) |
15 neonates with neonatal pneumonia 5 neonates with urinary tract infection 35 neonates with non-specific infection |
Piperacillin–tazobactam 100 mg/kg bid | 7 |
Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis 3 × 1.0 × 107 CFU/day |
7 | High-throughput sequencing of 16S rRNA amplicons |
| Engelbrektson et al. (2009) [62] | USA | placebo-controlledRCT | 40 (77.5) |
36.5 ± N.D. (39.5 ± N.D.) |
Healthy volunteers – no indication | Augmentin (amoxicillin and clavulanic acid) 875 mg bid | 7 |
Bifidobacterium lactis Bl-04 (5 × 109 CFU), Bifidobacterium lactis Bi-07 (5 × 109 CFU), Lactobacillus acidophilus NCFM (5 × 109 CFU) Lactobacillus paracasei Lpc-37 (5 × 109 CFU) and Bifidobacterium bifidum Bb-02 (5 × 108 CFU) 2 × 2.05 × 1010 CFU/day |
21 | DNA-based TRFLP analysis and culture-based microbiological techniques |
| Forssten et al. (2014) [63] | Finland | double-blinded, parallel RCT | 80 (50) |
33.7 ± 9.4 (30.9 ± 10.3) |
Healthy volunteers – no indication | Amoxicillin 875 mg, clavulanate 125 mg | 7 |
Lactobacillus acidophilus (L. acidophilus) ATCC 700396 and Bifidobacterium animalis (B. animalis) ssp. Lactis ATCC SD5220 (Danisco) 12.5 × 109 and 12.5 × 109 CFU/day |
14 | qPCR and flow cytometry |
| Madden et al. (2005) [57] | UK | pilot-scale, double-blinded RCT | 13 (53.8) |
60 ± N.D. (49 ± N.D.) |
Helicobacter pylori infection | Amoxycillin 500 mg qid, metronidazole 400 mg tid, lansoprazole 30 mg bid | 8 |
Lactobacillus acidophilus (CLT60 and CUL21) and two strains of Bifidobacterium bifidum (CUL17 and B. bifidum Rhodia 2.5 × 1010 CFU/day |
14 | Culture-based microbiological techniques |
| Plummer et al. (2005) [58] | UK | double-blinded RCT | 155 (N.D.) |
N.D. N.D. |
Helicobacter pylori infection | Amoxicillin 1 g bid, clarithromycin 500 mg bid, lansoprazole 30 mg bid; in case of penicillin allergy, metronidazole 400 mg tid was substituted | 7 |
Lactobacillus acidophilus (CUL60 and CUL21) and two strains of Bifidobacterium spp 2.5 × 1010 CFU/day |
21 | Culture-based microbiological techniques |
| Wang et al. (2017) [59] | China | double-blinded RCT | 20 (45) |
37.1 ± 12.3 (42.8 ± 13.8) |
Helicobacter pylori infection | Esomeprazole 20 mg bid, amoxicillin 1000 mg bid, clarithromycin 500 mg bid, tinidazole 500 mg bid | 14 |
Saccharomyces boulardii CNCM I-745® 2 × 500 mg |
14 | Culture-based microbiological techniques |
| Amarri et al. (2008) [60] | Italy | open-label, national, parallel RCT | 58 (50) | 40 ± 18.9 months (42.1 ± 18.9 months) | Bacterial upper respiratory tract infections | Amoxicillin 50 mg/kg/day divided in 3 daily doses | 5-10 |
Antibiotic-resistant Bacillus clausii 2 × 2 × 109 CFU/day |
12-17 | PCR-DGGE |
Abbreviations: RCT Randomized controlled trial, USA United States of America, UK United Kingdom, N.D. No data, bid Twice a day; tid, three times a day, qid Four times a day, bTEFAP Bacterial tag–encoded FLX amplicon pyrosequencing, DNA Deoxyribonucleic acid, TRFLP Terminal restriction fragment length polymorphism, qPCR Quantitative real-time polymerase chain reaction PCR-DGGE Polymerase chain reaction denaturing gradient gel electrophoresis, rRNA Ribosomal ribonucleic acid, CFU Colony forming unit
aIf not otherwise mentioned, the studies were single centers