Effects of Herbal and Natural Product Interventions on Gut Microbiota and Clinical Outcomes in Patients Receiving PPI-Containing Therapy: A Systematic Review and Meta-Analysis.
Herbal and natural product interventions may be associated with favorable clinical outcomes and potential microbiota-modulating effects in patients receiving PPI-containing therapy, but certainty remains limited due to methodological concerns, outcome indirectness, and heterogeneity.
Key Findings
Results
Herbal and natural product interventions were associated with significantly higher Helicobacter pylori eradication rates compared to control groups.
Analysis was based on 18 studies (17 randomized controlled trials, 1 observational study; n = 1984 participants)
Studies were identified from six databases (PubMed, EMBASE, Web of Science, Scopus, CENTRAL, and CNKI) searched from inception to March 2026
Results
The Chinese-style total effective rate was higher in herbal intervention groups compared to controls.
Pooled RR = 1.19, 95% CI 1.14–1.25
Heterogeneity was low at I2 = 0%
The authors note this outcome is non-standardized and should be interpreted cautiously
This outcome metric reflects a composite clinical assessment commonly used in Chinese clinical trials
Results
Exploratory microbiome meta-analyses suggested higher post-treatment levels of Bifidobacterium and Lactobacillus in herbal intervention groups.
These analyses were described as exploratory rather than confirmatory
Substantial heterogeneity limited interpretability of the microbiome findings
Results were not accompanied by pooled effect size statistics deemed sufficiently reliable for primary reporting
These genera are generally considered beneficial commensal bacteria
Results
Narrative synthesis revealed potential preservation of alpha-diversity and attenuation of pathobiont proliferation in herbal intervention groups.
These findings were reported through narrative synthesis rather than formal meta-analysis
Alpha-diversity is a measure of species richness and evenness within a microbial community
PPI-containing regimens, including bismuth quadruple therapy, may perturb gut microbiota through combined exposure to acid suppression, antibiotics, bismuth, and underlying disease context
The findings were considered exploratory given methodological limitations across included studies
Results
The overall certainty of evidence was limited due to methodological concerns, outcome indirectness, and heterogeneity across included studies.
Risk of bias was assessed using RoB 2.0 for randomized trials and ROBINS-I for the observational study
18 total studies were included: 17 randomized controlled trials and 1 observational study
The review was prospectively registered in PROSPERO (CRD420261346672)
The authors called for high-quality trials stratified by antibiotic exposure to address remaining uncertainty
What This Means
This research brings together evidence from 18 clinical studies involving nearly 2,000 patients to examine whether herbal medicines and natural products can help preserve healthy gut bacteria and improve treatment outcomes in people taking proton pump inhibitors (PPIs) — medications that reduce stomach acid, often used alongside antibiotics to treat H. pylori infections. The concern is that these treatment regimens can disrupt the natural balance of gut bacteria, potentially causing side effects and reducing the diversity of beneficial microbes. The researchers found that patients who received herbal or natural product supplements alongside their standard PPI-based therapy had about a 20% higher chance of successfully clearing H. pylori infection compared to those who did not receive these additions. There were also hints that beneficial bacteria like Bifidobacterium and Lactobacillus were better preserved in the herbal groups, and that overall bacterial diversity in the gut was less disrupted.
However, the researchers emphasize that these conclusions come with important caveats. Many of the included studies had methodological weaknesses, the ways outcomes were measured varied widely between studies, and some key findings showed substantial inconsistency across trials. One commonly reported outcome — the 'Chinese-style total effective rate' — is not a standardized international measure, making it difficult to interpret in a global context. As a result, while the overall direction of findings is encouraging, the authors describe the certainty of the evidence as limited.
This research suggests that herbal and natural product supplements may offer some benefit when added to standard acid-suppressing and antibiotic regimens, particularly for H. pylori eradication and gut microbiota preservation, but more rigorous and well-designed clinical trials are needed before firm recommendations can be made. Future studies should specifically account for antibiotic exposure, as this is a major factor affecting gut microbiota that was not consistently addressed in existing research.
Hwang J, Choi Y. (2026). Effects of Herbal and Natural Product Interventions on Gut Microbiota and Clinical Outcomes in Patients Receiving PPI-Containing Therapy: A Systematic Review and Meta-Analysis.. Nutrients. https://doi.org/10.3390/nu18111792