TY - JOUR
T1 - Proton pump inhibitor treatment aggravates bacterial translocation in patients with advanced cirrhosis and portal hypertension
AU - Sturm, Lukas
AU - Hirose, Misa
AU - Stolz, Laura
AU - Schultheiss, Michael
AU - Zoldan, Katharina
AU - Reincke, Marlene
AU - Huber, Jan Patrick
AU - Kaeser, Rafael
AU - Boettler, Tobias
AU - Thimme, Robert
AU - Albert, Elisabeth
AU - Busch, Hauke
AU - Künstner, Axel
AU - Bettinger, Dominik
N1 - Funding Information:
L.STU. and M.S. are supported by the Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Germany. A.K. and H.B. acknowledge computational support from the OMICS compute cluster at the University of Luebeck, Germany. The authors acknowledge support from the Open Access Publication Fund of the University of Freiburg, Germany.
Funding Information:
L.STU. and M.S. are supported by the Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Germany. A.K. and H.B. acknowledge computational support from the OMICS compute cluster at the University of Luebeck, Germany. The authors acknowledge support from the Open Access Publication Fund of the University of Freiburg, Germany. L.STU., D.B., study concept and design; L.STU., M.H., L.STO., M.S., K.Z., E.A., acquisition of data; L.STU., L.STO., A.K., analyses and interpretation of data; L.STU., D.B., drafting of the manuscript; M.S., M.R., J.H., R.K., T.B., R.T., critical revision of the manuscript for important intellectual content; H.B., D.B., supervision. All authors approved the final version of the article, including the authorship. The authors received funding from the Scientific Society, University of Freiburg, Germany. The authors have nothing to declare with regard to this work. Scientific Society University of Freiburg, Germany
Funding Information:
The authors received funding from the Society, University of Freiburg, Germany. The authors have nothing to declare with regard to this work.
Publisher Copyright:
Copyright © 2023 Sturm et a.
PY - 2023/10
Y1 - 2023/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85176741374&partnerID=8YFLogxK
U2 - 10.1128/MBIO.00492-23
DO - 10.1128/MBIO.00492-23
M3 - Journal articles
C2 - 37623323
AN - SCOPUS:85176741374
SN - 2161-2129
VL - 14
JO - mBio
JF - mBio
IS - 5
ER -