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Proton pump inhibitor treatment aggravates bacterial translocation in patients with advanced cirrhosis and portal hypertension
Recent studies have linked proton pump inhibitor (PPI) treatment to increased complications of cirrhosis, such as bacterial infections and hepatic encephalopathy. However, the underlying pathophysiological mechanisms remain unclear. The present study investigated the hypothesis that PPI treatment ma...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10653923/ https://www.ncbi.nlm.nih.gov/pubmed/37623323 http://dx.doi.org/10.1128/mbio.00492-23 |
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author | Sturm, Lukas Hirose, Misa Stolz, Laura Schultheiss, Michael Zoldan, Katharina Reincke, Marlene Huber, Jan Patrick Kaeser, Rafael Boettler, Tobias Thimme, Robert Albert, Elisabeth Busch, Hauke Künstner, Axel Bettinger, Dominik |
author_facet | Sturm, Lukas Hirose, Misa Stolz, Laura Schultheiss, Michael Zoldan, Katharina Reincke, Marlene Huber, Jan Patrick Kaeser, Rafael Boettler, Tobias Thimme, Robert Albert, Elisabeth Busch, Hauke Künstner, Axel Bettinger, Dominik |
author_sort | Sturm, Lukas |
collection | PubMed |
description | Recent studies have linked proton pump inhibitor (PPI) treatment to increased complications of cirrhosis, such as bacterial infections and hepatic encephalopathy. However, the underlying pathophysiological mechanisms remain unclear. The present study investigated the hypothesis that PPI treatment may promote adverse effects in patients with advanced cirrhosis by affecting subclinical bacterial translocation (BT) from the gut into the portal venous bloodstream. Blood samples from the portal vein were obtained during implantation of a transjugular intrahepatic portosystemic shunt (TIPS) in a total of 80 cirrhosis patients with PPI treatment (PPI group, n = 57) and without PPI treatment (no-PPI group, n = 23). BT was identified using a 16S ribosomal RNA gene (V1V2 region) polymerase chain reaction. The microbiota composition in the portal venous blood samples was further analyzed by deep amplicon sequencing. Indeed, the prevalence of BT was significantly higher in the PPI group compared to the no-PPI group (86.0% vs 52.2%, P = 0.001). Importantly, this effect was not attributable to group differences in the severity of cirrhosis, parameters of portal hypertension, or medication. Microbiome analyses showed significantly increased alpha-diversity (Shannon) in the portal venous blood of the PPI group. Taxonomic analyses revealed significantly increased Streptococcus abundances in these patients. The present study reveals aggravated BT in patients with advanced cirrhosis and portal hypertension receiving PPI therapy. Increased BT could be an important pathomechanism contributing to the adverse effects of PPI treatment in patients with cirrhosis. IMPORTANCE: Long-term prescription of proton pump inhibitors (PPIs) in patients with cirrhosis is common practice. However, in recent years, several observational studies have reported increased complications and negative prognostic effects of PPI treatment in these patients. Judging the significance of these associations is complicated by the fact that a plausible underlying pathomechanism has not been identified so far. In the present study, we address this important issue by investigating the impact of PPI treatment on subclinical bacterial translocation from the gut into the blood stream in patients with advanced cirrhosis and portal hypertension. Indeed, we report significantly aggravated bacterial translocation in cirrhosis patients receiving PPI treatment. This finding is highly relevant, as bacterial translocation is known to promote the development of complications and impair prognosis in patients with cirrhosis. Hence, the present study could establish a plausible link between PPI treatment and adverse effects in cirrhosis. |
format | Online Article Text |
id | pubmed-10653923 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-106539232023-08-25 Proton pump inhibitor treatment aggravates bacterial translocation in patients with advanced cirrhosis and portal hypertension Sturm, Lukas Hirose, Misa Stolz, Laura Schultheiss, Michael Zoldan, Katharina Reincke, Marlene Huber, Jan Patrick Kaeser, Rafael Boettler, Tobias Thimme, Robert Albert, Elisabeth Busch, Hauke Künstner, Axel Bettinger, Dominik mBio Research Article Recent studies have linked proton pump inhibitor (PPI) treatment to increased complications of cirrhosis, such as bacterial infections and hepatic encephalopathy. However, the underlying pathophysiological mechanisms remain unclear. The present study investigated the hypothesis that PPI treatment may promote adverse effects in patients with advanced cirrhosis by affecting subclinical bacterial translocation (BT) from the gut into the portal venous bloodstream. Blood samples from the portal vein were obtained during implantation of a transjugular intrahepatic portosystemic shunt (TIPS) in a total of 80 cirrhosis patients with PPI treatment (PPI group, n = 57) and without PPI treatment (no-PPI group, n = 23). BT was identified using a 16S ribosomal RNA gene (V1V2 region) polymerase chain reaction. The microbiota composition in the portal venous blood samples was further analyzed by deep amplicon sequencing. Indeed, the prevalence of BT was significantly higher in the PPI group compared to the no-PPI group (86.0% vs 52.2%, P = 0.001). Importantly, this effect was not attributable to group differences in the severity of cirrhosis, parameters of portal hypertension, or medication. Microbiome analyses showed significantly increased alpha-diversity (Shannon) in the portal venous blood of the PPI group. Taxonomic analyses revealed significantly increased Streptococcus abundances in these patients. The present study reveals aggravated BT in patients with advanced cirrhosis and portal hypertension receiving PPI therapy. Increased BT could be an important pathomechanism contributing to the adverse effects of PPI treatment in patients with cirrhosis. IMPORTANCE: Long-term prescription of proton pump inhibitors (PPIs) in patients with cirrhosis is common practice. However, in recent years, several observational studies have reported increased complications and negative prognostic effects of PPI treatment in these patients. Judging the significance of these associations is complicated by the fact that a plausible underlying pathomechanism has not been identified so far. In the present study, we address this important issue by investigating the impact of PPI treatment on subclinical bacterial translocation from the gut into the blood stream in patients with advanced cirrhosis and portal hypertension. Indeed, we report significantly aggravated bacterial translocation in cirrhosis patients receiving PPI treatment. This finding is highly relevant, as bacterial translocation is known to promote the development of complications and impair prognosis in patients with cirrhosis. Hence, the present study could establish a plausible link between PPI treatment and adverse effects in cirrhosis. American Society for Microbiology 2023-08-25 /pmc/articles/PMC10653923/ /pubmed/37623323 http://dx.doi.org/10.1128/mbio.00492-23 Text en Copyright © 2023 Sturm et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Sturm, Lukas Hirose, Misa Stolz, Laura Schultheiss, Michael Zoldan, Katharina Reincke, Marlene Huber, Jan Patrick Kaeser, Rafael Boettler, Tobias Thimme, Robert Albert, Elisabeth Busch, Hauke Künstner, Axel Bettinger, Dominik Proton pump inhibitor treatment aggravates bacterial translocation in patients with advanced cirrhosis and portal hypertension |
title | Proton pump inhibitor treatment aggravates bacterial translocation in patients with advanced cirrhosis and portal hypertension |
title_full | Proton pump inhibitor treatment aggravates bacterial translocation in patients with advanced cirrhosis and portal hypertension |
title_fullStr | Proton pump inhibitor treatment aggravates bacterial translocation in patients with advanced cirrhosis and portal hypertension |
title_full_unstemmed | Proton pump inhibitor treatment aggravates bacterial translocation in patients with advanced cirrhosis and portal hypertension |
title_short | Proton pump inhibitor treatment aggravates bacterial translocation in patients with advanced cirrhosis and portal hypertension |
title_sort | proton pump inhibitor treatment aggravates bacterial translocation in patients with advanced cirrhosis and portal hypertension |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10653923/ https://www.ncbi.nlm.nih.gov/pubmed/37623323 http://dx.doi.org/10.1128/mbio.00492-23 |
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