Background
H. pylori antibiotic resistance and current treatment regimens
First-line therapy
Second-line therapy
Third-line therapy
Drawbacks of antibiotic therapy against H. pylori
Probiotics as anti-H. pylori agents
Comprehensive definition of probiotics
Probiotic name | Potential activity | Human/animal/in-vitro examination | Country | Ref |
---|---|---|---|---|
L. salivarius WB1004 | Inhibition of colonization, lactic acid | BALB/c mice | Japan | [62] |
L. acidophilus (johnsonii) La1 | Inhibition of colonization, lactic acid, H2O2, bacteriocins | Human | Switzerland | [63] |
L. johnsonii La1 | Inhibition of colonization, lactic acid, H2O2, bacteriocins | Human | Switzerland | [64] |
L. acidophilus CRL 639 | Autolysins, lactic acid | In-vitro | Sweden | [65] |
L. gasseri OLL 2716 | Anti-inflammatory activity, lactic acid | Human | Japan | [66] |
L. reuteri | Anti-inflammatory activity (inhibition of IL-8 synthesis), lactic acid | In-vitro | Canada | [67] |
L. casei Shirota | Biocine, lactic acid, Inhibition of colonization | Human | Netherlands | [68] |
L. casei Shirota | Biocine, lactic acid, Inhibition of colonization | C57BL/6 mice | Greece | [69] |
L. brevis | Arginine deiminase activity, inhibition of colonization | Human | Italy | [70] |
L. rhamnosus R0011 and L. acidophilus R0052 | Inhibition of colonization, lactic acid | C57BL/6 mice | Canada | [71] |
L. salivarius | Lactic acid, bacteriocin | In-vitro | Ireland | [72] |
L. bulgaricus BB18 and Enterococcus faecium MH3 | Lactic acid, bulgaricin BB18, enterocin MH3 | In-vitro | Bulgaria | [73] |
L. brevis BK11 and E. faecalis BK61 | Lactic acid, bacteriocin | In-vitro | Korea | [74] |
L. lactis A164 and L. lactis BH5 | Lactic acid, lacticin A164, lacticin BH5 | In-vitro | Korea | [75] |
Bacillus clausii | inhibition of colonization (bacterial cell and spores) | Human | Italy | [76] |
B. subtilis | Amicoumacin A | In-vitro | France | [77] |
Lactobacilli and Bifidobacteria | Lactic acid | Human | Germany | [78] |
Weissella confusa PL9001 | Bacteriocin, inhibition of colonization | In-vitro | Korea | [79] |
E. faecium GM-1 | Lactic acid, bacteriocin? | In-vitro | South Korea | [80] |
E. faecium TM39 | Lactic acid, bacteriocin | In-vitro | Taiwan | [81] |
Saccharomyces boulardii | Anti-inflammatory activity | Human | Romania | [82] |
L. reuteri ATCC 55730 | Reuterin | Human | Italy | [83] |
L. rhamnosus JB3 | Antagonist of AI‐2 | In-vitro | Taiwan | [84] |
Substantial mechanism of probiotics against H. pylori infection
Competition for binding sites
Mucosal barrier
Probiotics as antibiotics
Co-aggregation and auto-aggregation (querish)
Immunomodulatory mechanism
Probiotics as delivery system for the treatment of H. pylori infection
Probiotics and animal models
Fist author | Year | Probiotic strain name | Dosage /duration | Animal model | Conclusion remarks | Ref |
---|---|---|---|---|---|---|
Ushiyama et al | 2003 | L. gasseri OLL2716 | 107 CFU/mL | BALB/c mice | Anti-H. pylori effects Reduction of IL-8 | [122] |
Sgouras et al | 2004 | L. casei Shirota | 108 CFU/mL, 9 months | C57BL/6 mice | Reducing H. pylori colonization and decrease specific IgG titer | [69] |
Henry et al | 2004 | L. rhamnosus R0011, L. acidophilus R0052 | 109 CFU/mL, 9 weeks | C57BL/6 mice | Anti-H. pylori effects Reduce gastric inflammation | [71] |
Pena et al | 2005 | L. reuteri 1602, L. paracasei 6798 | 109 CFU/mL, 12 weeks | C57BL/6 mice | Reducing the TNF-α and IL-12 levels | [123] |
Sgouras et al | 2005 | L. johnsonii La1 L. amylovorus CDE471 L. acidophilus IBB 801 | 1.5–4 × 108 CFU/mL, 3 months | C57BL/6 mice | Reducing H. pylori colonization and decrease gastric inflammation | [137] |
Brzozowski et al | 2006 | L. acidophilus R0052 L. rhamnosus R0011 | 2 × 109 CFU/mL, 2 weeks | Mongolian gerbil | Reduction gastrin and gastric inflammation | [138] |
Chenoll et al | 2011 | B. bifidum CECT 7366 | 109 CFU/mL | C57BL/6 mice | Blocking colonization of H. pylori | [139] |
Kuo et al | 2013 | L. acidophilus, B. lactis | 5 × 109 CFU/mL | Mongolian gerbil | Reduction of gastric inflammation | [140] |
Kaur et al | 2014 | P. acidilactici BA28 | 109 CFU/mL, 24 weeks | C57BL/6 mice | Anti-H. pylori | [141] |
Kim et al | 2014 | P. pentosaseus (SL4) | 108 CFU/mL, 6 weeks | C57BL/6 mice | Anti-H. pylori | [142] |
Zaman et al | 2014 | L. reuteri L. johnsonii L. murinus | 109 CFU/mL | Mongolian gerbil | Anti-H. pylori | [143] |
Matsui et al | 2015 | L. gasseri SBT2055 | 109 CFU/mL | C57BL/6 mice | Production of specific IgA, Blocking progression of MALT | [144] |
Yu et al | 2015 | E. faecalis B. longum L. acidophilus | 107 CFU/mL | C57BL/6 mice | Reducing gastric inflammation | [145] |
Pan et al | 2016 | L. plantarum ZDY 2013 | 109 CFU/mL | C57BL/6 mice | Reducing gastric inflammation | [146] |
Afsahi et al | 2018 | L. plantarum ATCC8014 | 106 CFU/mL, 2 weeks | C57BL/6 mice | Anti-H. pylori Reduction of gastric inflammation | [147] |
Chen et al | 2018 | L. rhamnosus JB3 | 5 × 107 CFU/mL | C57BL/6 mice | Anti-H. pylori Reduction of gastric inflammation | [148] |
Merino et al | 2018 | L. fermentum UCO-979C | 107 CFU/mL | Mongolian gerbil | Inhibited H. pylori SS1 | [149] |
Lin et al | 2020 | L. fermentum P2 (P2), L. casei L21 (L21), L. rhamnosus JB3 (JB3) | 107 CFU/mL | C57BL/6 mice | Reduction of gastric inflammation | [150] |
Probiotics as adjuvant therapy
Therapeutic effects of probiotics against H. pylori infection in children
First author | Year | Type of study | Eradication therapy | Probiotic regimen | Duration | Cure rate | Statistical significance | Ref | |
---|---|---|---|---|---|---|---|---|---|
Case | Control | ||||||||
Gotteland et al | 2005 | Open randomized | NA | Saccharomyces boulardii, L. acidophilus | 8 weeks | 12%, 6.5% | 0% | p < 0.000 | [152] |
Sykora et al | 2005 | Double blind randomized | Omeprazole, amoxicillin, clarithromycin for 7 days | L. casei DN-114 001 | 2 weeks | 84.6% | 57.4% | p = 0.0019 | [156] |
Goldman et al | 2006 | Double blind randomized | Omeprazole, amoxicillin, clarithromycin for 7 days | B. animalis + L. casei | 3 months | 45.4% | 37.5% | p < 0.01 | [157] |
Lionetti et al | 2006 | Double blind randomized | Omeprazole, amoxicillin, clarithromycin, tinidazole (sequential therapy) | L. reuteri ATCC 55,730 | 20 days | 85% | 80% | p < 0.009 | [158] |
Gotteland et al | 2008 | Double blind randomized | NA | L. jonsonii La1 plus cranberry, L. jonshonii La1, cranberry plus heat-killed L. jonsonii La1 | 3 weeks | 22.9%, 14.9%, 16.9% | 1.5% | p = 0.542 | [159] |
Hurduc et al | 2009 | Open randomized | Omeprazole, amoxicillin, clarithromycin for 7 days | Saccharomyces boulardi | 4 weeks | 93.7% | 80.9% | p < 0.002 | [82] |
Szajewska et al | 2009 | Double blind randomized | Omeprazole, amoxicillin, clarithromycin for 7 days | L. rhamnosus GG | 1 weeks | 67.6% | 68.7% | Not significant | [160] |
Boonyaricaikij et al | 2009 | Single blind | NA | L. gasseri OLL2716 | 1 years | 29.3% | 6.6% | p = 0.03 | [161] |
Tolone et al | 2012 | NA | Omeprazole, amoxicillin, clarithromycin for 7 days | Probinul-Cadigroup | NA | 88.2% | 76.4% | p < 0.05 | [162] |
Zhao et al | 2014 | prospective randomized controlled study | Omeprazole, amoxicillin, clarithromycin for 7 days | Saccharomyces boulardii | 7 days | 85% | 75.8% | p < 0.05 | [163] |
Wang et al | 2014 | NA | Omeprazole, amoxicillin, clarithromycin for 7 days | L. acidophilus, B. bifidum | 2 weeks | 83.7% | 64.4% | p < 0.05 | [164] |
Akcam et al | 2015 | Open randomized | triple therapy (lansoprazole, amoxicillin, clarithromycin for 14 days) | L. casei, L. acidophilus, B. lactis | 2 weeks | 66.6% | 68.9% | p = 0.78 | [165] |
Zhu etal | 2017 | Double blind randomized | Sequential, Triple therapy | Sequential-Lactobacillus, triple-Lactobacillus therapy | NA | Sequential-Lactobacillus and triple-Lactobacillus better than any of them alone (P < 0.05) | p < 0.01 | [166] |
Therapeutic effects of probiotics against H. pylori infection in adults
First author | Year | Sample size | Eradication regimen | Probiotics | Conclusion remarks | Significance | Ref |
---|---|---|---|---|---|---|---|
Tong et al | 2007 | 1671 | First-line and second-line therapy (triple and bismuth containing quadruple therapy) | B. clausii, Lactobacillus, Saccharomyces | ER: RR: 1.84; 95% CI: 1.34–2.54 AE: 0.44; 95% CI: 0.3–0.6 | Both significant AE was adverse event ER was eradication rate | [169] |
Sachdeva et al | 2009 | 963 | First-line therapy (Triple and Quadruple) | Lactobacillus, Bifidobacterium | ER: 1.91; 95% CI: 1.3–2.6 AE: 0.51; 95% CI: 0.1–2.5 but AE was not significant | Reduction of adverse event rate was not significant | [170] |
Zou et al | 2009 | 1372 | First-line therapy (Triple) | Lactobacillus | ER: 1.78; 95% CI: 1.21–2.62 AE: OR was 0.49 (95% CI = 0.24–1.02) | Both significant | [171] |
Szajewska et al | 2010 | 1307 | First-line therapy (Triple) | S. boulardii | ER: 1.13, 95% CI 1.05–1.21 AE: RR 0.46, 95% CI 0.3–0.7 | Both significant | [172] |
Zheng et al | 2013 | 1163 | First-line therapy (Triple) | Lactobacillus | RR: 1.14; 95% CI: 1.06–1.22 (significant increase of eradication rate) but no significant reduction of overall adverse event | Reduction of adverse event rate was not significant | [173] |
Wang et al | 2013 | 1469 | First-line and second-line therapy (triple and bismuth containing quadruple therapy) | Bifidobacterium, Lactobacillus | ER: 2.066 (95% CI, 1.398–3.055 AE: 0.305; 95% CI, 0.117–0.793) | Both significant | [174] |
Zhu et al | 2014 | 2259 | standard triple H. pylori | Lactobacillus, Bifidobacterium, Saccharomyces | ER: 1.67 (95%CI: 1.38–2.02) AE: (OR = 0.49, 95%CI: 0.26–0.94 | Both significant | [175] |
Dang et al | 2014 | 4459 | First-line therapy (Triple) | L. acidophilus, L. casei DN-114001, L. gasseri, Bifidobacterium infantis 2036 | Curing rate was significantly increase in probiotics (RR: 1.11; 95%CI: 1–1.1) as well as reduce of adverse event (RR: 0.73; 95%CI: 0.5–0.9) | Both significant | [176] |
Zhang et al | 2015 | 6997 | First-line and second-line therapy (triple And bismuth containing quadruple therapy) | Lactobacillus, Bifidobacterium, Streptococcus, Saccharomyces, Enterococcus, Bacillus | ER: RR = 1.13; 95%CI: 1.10–1.16 AE: RR = 0.59; 95%CI: 0.48–0.71 | Both significant | [177] |
Lu et al | 2016 | 3349 | First-line therapy (triple) | Lactobacilli, Bifidobacteria, Bacillus clausii, E. faecium | ER: OR 1.44, 95% CI: 0.87, 2.39 but not significant AE: probiotics did improve the adverse effects OR 0.56, 95% CI: 0.31, 1.01 | Both not significant | [178] |
Lu et al | 2016 | 2306 | First-line therapy (Triple) | Lactobacillus, Bifidobacterium | Eradication rate in probiotic supplementation group was significantly higher than control (RR: 1.15; 95%CI: 1.1–1.2) and reducing adverse event (RR: 0.71; 0.5–0.9) probiotic supplementation increased eradication of triple therapy in both 7 and 14-days | Both significant | [179] |
Si et al | 2017 | 2466 | First-line therapy (bismuth containing quadruple therapy) | Lactobacillus | Eradication rate was significant increase in probiotics (89% vs. 84.7% for first-line) (91% vs. 73.8% for second-line) | significant | [180] |
Losurdo et al | 2018 | NA | NA | Lactobacillus | ER: UBT value: 8.61% vs. 0.19% AE: 1, 95%CI: 0.06–18.08 not siginificANT FOR AE | Reduction of adverse event rate was not significant | [181] |
Shi et al | 2019 | 8924 | First-line therapy (Triple and Quadruple) | Lactobacillus | RR: 1.14; 95%CI: 1.10–1.18 (significant increase of eradication rate) and reduced side effects | Both significant | [182] |
Yu et al | 2019 | 724 | First-line therapy (Triple | Lactobacillus | Eradication rate was significantly increase in Lactobacillus supplement group (RR: 1.1; 95%CI: 1–1.2) and derease significantly adverse event (RR: 0.36; 95%CI: 0.1–0.7) | Both significant | [183] |
Pourmasoumi et al | 2019 | 525 | First-line therapy (Triple and Quadruple) | Lactobacillus, Bifidobacterium Saccharomyces | Eradication: RR: 1.28; 95% CI: 1.15–1.43 Adverse: RR: 0.90; 95% CI: 0.69–1.16 | Both significant | [184] |
Zhou et al | 2019 | 3592 | First-line therapy (Triple) | S. boulardii | ER: 1.09, 95% CI:1.05‐1.13 AE: RR = 0.33, 95%CI:0.16‐0.69 | Both significant | [185] |
Use of probiotics in the prevention of H. pylori infection
Diversity of gut microbiota during H. pylori treatment with probiotic supplementation
Row | Identifier | Start year | Participants | Allocation | Intervention model | Masking | Primary Purpose | Status | Country |
---|---|---|---|---|---|---|---|---|---|
1 | NCT04319991 | 2019 | 100 | Randomized | Parallel assignment | Single (Participant) | Supportive Care | Recruiting | Taiwan |
2 | NCT01115296 | 2010 | 100 | Randomized | Parallel assignment | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) | Treatment | Unknown | Italy |
3 | NCT03150394 | 2017 | 80 | Randomized | Parallel assignment | Double (Participant, Investigator) | Treatment | Unknown | Spain |
4 | NCT04178187 | 2019 | 800 | Randomized | Parallel assignment | Single (Participant) | Treatment | Recruiting | Greece |
5 | NCT01969331 | 2008 | 804 | Randomized | Parallel assignment | Triple (Participant, Care Provider, Investigator) | Treatment | Completed | Croatia |
6 | NCT02645201 | 2016 | 0 | Randomized | Parallel assignment | Triple (Participant, Care Provider, Investigator) | Treatment | Withdrawn | Belgium, Croatia, Germany, Israel, Slovenia |
7 | NCT03220542 | 2016 | 360 | Randomized | Factorial assignment | Single (Participant) | Treatment | Unknown | Korea |
8 | NCT03722433 | 2018 | 200 | Randomized | Parallel assignment | Double (Participant, Care Provider) | Treatment | Unknown | Taiwan |
9 | NCT03997279 | 2019 | 200 | Randomized | Parallel assignment | Triple (Participant, Care Provider, Investigator) | Treatment | Unknown | Sebria |
10 | NCT03377933 | 2019 | 40 | N/A | Single group assignment | None (Open Label) | Treatment | Unknown | China |
11 | NCT04473079 | 2020 | 100 | Randomized | Parallel assignment | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) | Supportive Care | Recruiting | Thailand |
12 | NCT04527055 | 2020 | 252 | Randomized | Parallel Assignment | Single (Outcomes Assessor) | Treatment | Enrolling by invitation | Taiwan |
13 | NCT03297242 | 2017 | 30 | N/A | N/A | N/A | N/A | Unknown | China |
14 | NCT04786938 | 2016 | 63 | Randomized | Parallel assignment | Single (Participant) | Treatment | Completed | Ecuador |
15 | NCT02689583 | 2016 | 3000 | Randomized | Parallel assignment | Single (Participant) | Treatment | Unknown | China |
16 | NCT03688828 | 2018 | 776 | Randomized | Parallel assignment | Triple (Participant, Investigator, Outcomes Assessor) | Treatment | Recruiting | China |
17 | NCT03404440 | 2016 | 56 | Randomized | Parallel assignment | Double (Participant, Investigator) | Treatment | Completed | Italy |
18 | NCT01456728 | 2011 | 56 | Randomized | Parallel assignment | Double (Participant, Investigator) | Treatment | Completed | Bulgaria |
19 | NCT02051348 | 2014 | 24 | Non-Randomized | Crossover assignment | Single (Participant) | Treatment | Completed | Ireland |