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Table 1 The main characteristics of the included studies

From: Probiotic supplementation during antibiotic treatment is unjustified in maintaining the gut microbiome diversity: a systematic review and meta-analysis

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

  1. 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
  2. aIf not otherwise mentioned, the studies were single centers