Systems biology analysis of omeprazole therapy in cirrhosis demonstrates significant shifts in gut microbiota composition and function
Open accessAbstract
Proton pump inhibitors (PPI) have been associated with infectious complications in cirrhosis, but their impact on distal gut microbiota composition and function is unclear. We aimed to evaluate changes in stool microbiota composition and function in patients with cirrhosis and healthy controls after omeprazole therapy. Both 15 compensated cirrhotic patients and 15 age-matched controls underwent serum gastrin measurement, stool microbiota profiling with multitagged pyrosequencing, and urinary metabolic profiling with NMR spectroscopy to assess microbial cometabolites before/after a 14-day course of 40 mg/day omeprazole under constant diet conditions. Results before (pre) and after PPI were compared in both groups, compared with baseline by systems biology techniques. Adherence was >95% without changes in diet or MELD (model for end-stage liver disease) score during the study. Serum gastrin concentrations significantly increased after PPI in cirrhosis (pre 38.3 ± 35.8 vs. 115.6 ± 79.3 pg/ml P < 0.0001) and controls (pre 29.9 ± 14.5 vs. 116.0 ± 74.0 pg/ml, P = 0.001). A significant microbiota change was seen in both controls and cirrhosis after omeprazole (QIIME P < 0.0001). Relative Streptococcaceae abundance, normally abundant in saliva, significantly increased postomeprazole in controls (1 vs. 5%) and cirrhosis (0 vs. 9%) and was correlated with serum gastrin levels ( r = 0.4, P = 0.005). We found significantly reduced hippurate in cirrhosis vs. controls both pre- and postomeprazole and increased lactate in both groups post vs. preomeprazole, whereas dimethylamine (DMA) decreased in cirrhosis only. On correlation network analysis, significant changes in linkages of bacteria with metabolites (hippurate/DMA/lactate) were found postomeprazole, compared with pre-PPI in cirrhosis patients. In conclusion, omeprazole is associated with a microbiota shift and functional change in the distal gut in patients with compensated cirrhosis that could set the stage for bacterial overgrowth.
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Cross-sectional and intervention studies have demonstrated a significant impact on the gut microbiota by proton-pump inhibitors.
“Moreover, cross-sectional as well as intervention studies have demonstrated a significant impact on the gut microbiota by proton-pump inhibitors36–38.”
From The gut microbiome in atherosclerotic cardiovascular disease (2017) · cites this paper as [36]
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- Authors
- Bajaj, J. S., Cox, I. J., Betrapally, N. S., Heuman, D. M., Schubert, M. L., Ratneswaran, M., Hylemon, P. B., White, M. B., Daita, K., Noble, N. A., Sikaroodi, M., Williams, R., Crossey, M. M. E., Taylor-Robinson, S. D., & Gillevet, P. M.
- Affiliations
- Virginia Commonwealth University (US)
- Foundation for Liver Research (GB)
- George Mason University (US)
- Imperial College London (GB)
- Corresponding author
- Bajaj, Jasmohan S.
- ORCID
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2014-11-15
- Volume
- 307
- Issue
- 10
- Pages
- G951-G957
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- PMC
- PMC4233285
- OpenAlex
- W2058793213
- Cited by
- 143
- References
- 31
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 12 · 2020: 22 · 2019: 15 · 2018: 19 · 2017: 19 · 2016: 11 · 2015: 19
- FWCI
- 6.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R01AA020203)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK087913)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- omeprazole, proton pump inhibitors, liver cirrhosis, gut microbiota, serum gastrin, Streptococcaceae, hippurate, dimethylamine, lactate, urinary metabolites, bacterial overgrowth, microbial metabolites, correlation network analysis
- MeSH terms
- Arginine, Feces, Female, Gastrins, Hippurates, Humans, Intestines, Liver Cirrhosis, Male, Middle Aged, Magnetic Resonance Spectroscopy, Omeprazole, Risk Factors, Time Factors, Biomarkers, Case-Control Studies, Treatment Outcome, Lactic Acid, Systems Biology, Proton Pump Inhibitors, Metabolomics, Microbiota
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