Biomarkers for oralization during long-term proton pump inhibitor therapy predict survival in cirrhosis
Open accessAbstract
Proton pump inhibitors (PPI) are an invaluable therapy option for acid related diseases; however, PPI therapy is also linked to a series of side effects in cirrhosis, such as microbiome alterations, spontaneous bacterial peritonitis and hepatic encephalopathy. Decision tools to balance benefits and risks of PPI therapy are largely missing. In this study, we tested gut-derived biomarkers to identify PPI-associated dysbiosis, its association with gut barrier function and liver-related mortality. In this observational study, faecal microbiome composition data obtained from 16S rDNA sequencing of 90 cirrhotic patients with and without long-term PPI use and additional potential biomarkers identified from the literature were evaluated for their predictive value regarding PPI-associated dysbiosis and liver-related three-year mortality. In addition, faecal calprotectin, faecal zonulin and serum lipopolysaccharides were assessed as markers for intestinal inflammation, gut permeability and bacterial translocation. Streptococcus salivarius, Veillonella parvula and the genus Streptococcus were significantly increased in patients with long-term PPI therapy and performed well as biomarkers for PPI-associated dysbiosis (accuracy: 74%, 72% and 74%, respectively). The abundance of Streptococcus salivarius was linked to intestinal inflammation and gut barrier dysfunction, whereas the abundance of Veillonella parvula showed associations with liver disease severity; both were independent predictors for liver-related three-year mortality. Gut-derived biomarkers of PPI-associated dysbiosis are linked to worse outcome and a potential option to evaluate the risks of adverse events during long-term PPI therapy.
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PPI use is connected to fecal microbiota oralization and worse anti-PD-1 outcomes.
“As previously reported, they also link PPI use with fecal microbiota oralization32 and adverse outcomes in response to anti-PD-1 therapy33.”
From Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1 (2022) · cites this paper as [32]
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- Authors
- Horvath, A., Rainer, F., Bashir, M., Leber, B., Schmerboeck, B., Klymiuk, I., Groselj-Strele, A., Durdevic, M., Freedberg, D. E., Abrams, J. A., Fickert, P., Stiegler, P., & Stadlbauer, V.
- Affiliations
- Medical University of Graz (AT)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Horvath, Angela
- ORCID
- Venue
- Scientific Reports
- Published
- 2019-08-19
- Volume
- 9
- Issue
- 1
- Pages
- 12000-12000
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6700098
- OpenAlex
- W2968783145
- Cited by
- 93
- References
- 44
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 10 · 2023: 16 · 2022: 12 · 2021: 17 · 2020: 13 · 2019: 1
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Austrian Science Fund (P24362)
- 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
- proton pump inhibitors, liver cirrhosis, gut dysbiosis, oralization, fecal microbiota, Streptococcus salivarius, Veillonella parvula, Streptococcus, liver-related mortality, intestinal barrier dysfunction, intestinal inflammation, bacterial translocation, fecal calprotectin, serum lipopolysaccharide, hepatic encephalopathy, spontaneous bacterial peritonitis
- MeSH terms
- Gastrointestinal Microbiome, Aged, Feces, Female, Humans, Intestinal Mucosa, Liver Cirrhosis, Male, Middle Aged, Mortality, Prognosis, Biomarkers, Proportional Hazards Models, Treatment Outcome, Proton Pump Inhibitors, Dysbiosis
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