Probiotics have long been proposed as a way to soften these side effects, potentially by attenuating antibiotic-induced disruption of the gut microbiota, reinforcing colonization resistance, and modulating mucosal immune responses. Previous meta-analyses, however, pooled trials that mixed proton pump inhibitors, vonoprazan, and other acid suppressants with different antibiotic backbones, probiotic strains, doses, and durations. That heterogeneity, the review authors argued, obscured what probiotics actually add when the underlying regimen is otherwise fixed.

To answer that narrower question, the team searched eight bibliographic databases and three trial registries from inception through mid-July 2026, with no language restrictions. Eligible studies were randomized controlled trials in adults with confirmed H. pylori infection comparing a vonoprazan-based regimen plus a probiotic against the identical regimen without one, with probiotic administration overlapping the eradication course. The searches identified 506 database records and 19 registry records; after screening, sixteen reports corresponding to nine independent randomized studies met the criteria, encompassing 1,270 participants.

All nine trials were conducted in China, one multicenter and eight single-center, published or completed between 2023 and 2026. Six evaluated vonoprazan-amoxicillin dual therapy, one vonoprazan-based triple therapy, and two bismuth-containing quadruple therapy, with treatment durations of 10 days, 14 days, or, in one atypical case, four weeks. The probiotic interventions were biologically diverse, ranging from Bacillus subtilis plus Enterococcus faecium and Saccharomyces boulardii to compound lactic acid bacteria, Bifidobacterium capsules, Bacillus licheniformis, and a Bifidobacterium tetravaccine.

Eradication was generally confirmed by urea breath testing at least four weeks after treatment. Statistically, the team pooled risk ratios using restricted maximum-likelihood random-effects models with Hartung-Knapp confidence intervals, and reported 95 percent prediction intervals to estimate what a future comparable trial might show. The primary outcome was the proportion of participants experiencing at least one adverse event, treated as a participant-level binary measure rather than a count of episodes.

The reviewers used the Cochrane Risk of Bias 2 tool for outcome-specific bias assessments and GRADE to rate certainty, and excluded studies with ambiguous adverse-event totals or serious allocation concerns from the primary analyses. The tolerability signal was striking. Across five studies involving 611 participants, adjunctive probiotics reduced the risk of experiencing at least one adverse event by roughly 70 percent (risk ratio 0.30, 95 percent confidence interval 0.17 to 0.53; P = 0.004), with zero statistical heterogeneity.

The prediction interval, 0.12 to 0.79, remained entirely below the null, suggesting benefit would be expected in a future similar trial. Translated into absolute terms, the risk fell from 261 to about 79 per 1,000 treated, meaning roughly one additional patient avoids an adverse event for every six given probiotics. Sensitivity analyses kept the estimate between 0.31 and 0.38, and GRADE certainty was rated moderate.

The efficacy picture was far less convincing. Intention-to-treat eradication across seven studies and 910 participants showed a small apparent benefit (risk ratio 1.09, 95 percent confidence interval 1.00 to 1.19), but the prediction interval of 0.92 to 1.30 crossed no effect, and statistical significance vanished in sensitivity analyses that excluded dissertation-based or methodologically atypical studies. Per-protocol eradication showed little or no difference (risk ratio 1.03), and adherence, already high at about 95 percent in control groups, was not clearly improved.

Individual symptoms such as constipation, bloating, and nausea trended in probiotics' favor, but these analyses rested on few events and were graded very-low-certainty. Discontinuation and serious adverse events were too rare to yield interpretable estimates. The authors caution that all included trials were conducted in China, and that regional differences in antimicrobial resistance, prior antibiotic exposure, diet, baseline microbiota, probiotic product quality, and symptom-reporting behavior may limit generalizability to other populations.

Most trials were also open-label, a concern for subjectively reported adverse events, and the data cannot identify an optimal probiotic strain, dose, or timing. The reviewers conclude that probiotics are best framed as supportive care to improve tolerability during vonoprazan-based therapy, not as a means of raising cure rates, and they call for adequately powered, placebo-controlled, multicenter trials with standardized outcome definitions and strain-level reporting to confirm the findings in diverse settings.

Subject of Research: Adjunctive probiotics during vonoprazan-based Helicobacter pylori eradication therapy

Article Title: Adjunctive probiotics may reduce adverse events during vonoprazan-based Helicobacter pylori eradication: a systematic review and meta-analysis

Article References: Lin, C.-J., Ren, P.-Y., Chen, H.-Y., Zheng, M.-Q., Jiang, Y.-X., Li, G., Fu, M., & Guo, Y.-H. (2026). Adjunctive probiotics may reduce adverse events during vonoprazan-based Helicobacter pylori eradication: a systematic review and meta-analysis. Frontiers in Pharmacology, 17, Article 1946885. https://doi.org/10.3389/fphar.2026.1946885

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1946885

Keywords: Helicobacter pylori, vonoprazan, probiotics, meta-analysis, adverse events, eradication therapy, gut microbiota, potassium-competitive acid blocker, tolerability, randomized controlled trials, GRADE certainty, gastroenterology