Proton pump inhibitor in upper gastrointestinal fecal microbiota transplant: A systematic review and analysis
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Updated: Jan 2, 2026
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Published on: April 6, 2022
Annie S Hong1,2, Wen Yuan Yu1,2, Jenny M Hong1
1University of Nevada Las Vegas School of Medicine, Las Vegas, Nevada, USA.
Background And Aims:
Fecal microbiota transplantation (FMT) is used in recurrent Clostridioides difficile infections. However, protocols are facility dependent, and one variable is whether pre-procedural proton pump inhibitors (PPIs) are given. In theory, PPIs reduce acidity and protect the transplanted microbiome for the most potent dose. We conducted a systematic review to study the effect of PPIs on FMT delivered by upper gastrointestinal (GI) routes.
Methods:
We searched Pubmed/Medline, Cochrane Library, Embase, Scopus, and Web of Science through December 16, 2018 using variations of keywords "fecal microbiota transplant" and "Clostridium difficile infection." Two authors independently reviewed 4210 results and found 11 qualifying studies with data on upper GI FMT, use of PPIs, and the rate of treatment failure at follow-up.
Results:
Of 233 included patients, treatment failure occurred in 20.6% of those with use of PPIs versus 22.6% in the group without (relative risk 0.91; confidence interval 0.56-1.50). Limitations include the lack of studies directly comparing outcomes based on use of PPIs and inability to control for possible confounders such as chronic PPI use, amount of stool transplanted, and pre-FMT antibiotics.
Conclusions:
We did not find evidence supporting a clinically significant benefit from routine use of PPIs in FMT protocol. It is possible that the theoretical benefit from improved survival of transplanted microbiota is offset by negative effects on the microbiome. We suggest that routine use of PPIs in upper GI FMT be reconsidered. Further investigation is needed to optimize protocols for safety and efficacy.
Insights
Proton pump inhibitors (PPIs) do not appear to significantly benefit fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infections when delivered via the upper gastrointestinal tract. Further research is needed to optimize FMT protocols for improved safety and efficacy.
Area of Science:
- Gastroenterology
- Microbiology
- Pharmacology
Background:
- Fecal microbiota transplantation (FMT) is a key treatment for recurrent Clostridioides difficile infections.
- Current FMT protocols vary, with the use of proton pump inhibitors (PPIs) before upper gastrointestinal (GI) delivery being a point of divergence.
- PPIs are theoretically proposed to enhance transplanted microbiome survival by reducing gastric acidity.
Purpose of the Study:
- To systematically review the impact of pre-procedural proton pump inhibitors (PPIs) on the efficacy of fecal microbiota transplantation (FMT) delivered via upper gastrointestinal routes for recurrent Clostridioides difficile infections.
Main Methods:
- A systematic literature search was conducted across major databases (PubMed/Medline, Cochrane Library, Embase, Scopus, Web of Science) up to December 16, 2018.
- Keywords included variations of "fecal microbiota transplant" and "Clostridium difficile infection."
- Eleven studies involving 233 patients met the inclusion criteria, providing data on upper GI FMT, PPI use, and treatment failure rates.
Main Results:
- Treatment failure occurred in 20.6% of patients who received PPIs compared to 22.6% in those who did not (Relative Risk: 0.91; 95% Confidence Interval: 0.56-1.50).
- No statistically significant difference in treatment outcomes was observed between the PPI and non-PPI groups.
- Limitations include a lack of direct comparative studies and potential confounding factors such as chronic PPI use and antibiotic pre-treatment.
Conclusions:
- The current evidence does not support a clinically significant benefit from the routine use of PPIs in upper GI FMT protocols for recurrent Clostridioides difficile infections.
- The theoretical advantage of PPIs in protecting the transplanted microbiota may be counteracted by potential negative impacts on the microbiome.
- Reconsideration of routine PPI use in upper GI FMT is suggested, with a call for further research to optimize FMT protocols for enhanced safety and efficacy.
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