The impact of probiotics on Helicobacter pylori eradication with bismuth quadruple therapy: A systematic review and meta-analysis

Background

Bismuth quadruple therapy (BQT) remains a cornerstone of first-line Helicobacter pylori eradication. However, its efficacy is increasingly undermined by antibiotic resistance, while frequent adverse events reduce its tolerability. Probiotics have been proposed as adjunctive agents to improve eradication outcomes and mitigate side effects, though their specific role in combination with BQT has yet to be fully established.

Methods

We conducted an extensive search of PubMed, Embase, Web of Science, and Cochrane Library for randomized controlled trials (RCTs) published through November 2024. Eligible studies compared H. pylori eradication rates and adverse events between probiotic-supplemented BQT (PBQT) and standard BQT in infected patients.

Results

Nineteen randomized controlled trials with 2973 samples were included. PBQT significantly improved H. pylori eradication rates compared to BQT alone (pooled odds ratio [OR] = 1.49, 95% confidence interval [CI] 1.20–1.85; P = 0.0004), with low heterogeneity (I² = 0%). Subgroup analyses demonstrated that both Saccharomyces boulardii (OR = 1.62; P < 0.05) and multi-strain probiotics (OR = 1.66; P < 0.05) significantly enhanced eradication rates. Concomitant administration of probiotics with antibiotics also yielded significant benefits (OR = 1.48, 95% CI 1.14–1.92; P = 0.003). PBQT demonstrated superior efficacy in the initial-treatment subgroup (OR = 1.48; P = 0.003) and among patients aged ≥18 y (OR = 1.47; P = 0.005). Regional subgroup analysis revealed a significant improvement in eradication rates for studies conducted in East Asia (OR = 1.66; P = 0.003). Antibiotic-specific subgroup analysis indicated a significant benefit of probiotics in the amoxicillin-clarithromycin BQT subgroup (OR = 1.59; P = 0.01). Overall, adverse events were significantly lower in the PBQT group (OR = 0.44, 95% CI 0.27–0.70, P = 0.0006), especially diarrhoea (OR = 0.33, 95% CI 0.21–0.52, P < 0.00001) and nausea (OR = 0.29, 95% CI 0.11–0.79, P = 0.02).

Conclusions

Adding probiotics, particularly S. boulardii or multi-strain combinations, to BQT significantly improves eradication efficacy and decreases treatment-related adverse events. PBQT represents a pragmatic optimization of current first-line regimens and supports its incorporation into clinical practice to improve H. pylori treatment outcomes.