The impact of proton pump inhibitors on the intestinal microbiota in chronic hepatitis C patients

Abstract

Objectives: Proton pump inhibitors (PPI), a class of drugs commonly used, are known to be associated with changes in the intestinal microbiota. Published studies were done in heterogeneous cohorts which could hamper conclusions drawn as effects of diseases were not taken into consideration. We aimed to elucidate differences in the intestinal microbiota being associated to the use of PPI in a cohort study of patients with chronic hepatitis C.

Material and Methods: The 16S rDNA gene was analyzed in stool samples of patients with and without PPI use. Patients with concomitant medication influencing the microbiota were excluded. Results were compared with the clinical course of hepatitis C patients with decompensated liver cirrhosis.

Results: No differences in alpha diversity could be observed, while the microbial community structure differed significantly, especially in patients with liver cirrhosis. The relative abundance of Streptococcus spp., Enterobacter spp. and Haemophilus spp. was significantly increased in patients with PPI use irrespectively of the stage of liver disease. Finally, in patients with decompensated liver cirrhosis due to chronic HCV infection only in these using PPI bacterial phylotypes were isolated.

Conclusions: PPI use was associated with significant alterations in the microbial community in patients with chronic hepatitis C, which were even pronounced in patients with liver cirrhosis. In patients with decompensated liver cirrhosis due to chronic HCV infection, the use of PPI may promote infections either directly or indirectly through changes in the microbial community structure. Future studies should further investigate long-term impact on the microbiota and the clinical outcome.

Keywords:

• Hepatitis C virus
• infections
• microbiota
• liver cirrhosis
• proton pump inhibitors

Disclosure statement

Benjamin Maasoumy has received speaker and/or consulting fees from Abbott Molecular, Roche, MSD/Merck, BMS, Fujirebio, Janssen-Cilaq, research support from Roche and Abbott Molecular, travel grants from Janssen-Cilaq and Gilead. Heiner Wedemeyer has been in Advisory Committees or Review Panels for Transgene, MSD, Roche, Gilead, Abbott, BMS, Falk, Abbvie, Novartis, GSK and Roche Diagnostics and has received Grant/Research Support from MSD, Novartis, Gilead, Roche, Abbott and Roche Diagnostics and Speaking and Teaching fees from BMS, MSD, Novartis, ITF, Abbvie and Gilead. Markus Cornberg has received personal fees from Abbvie, personal fees from Bristol-Myers Squibb, personal fees from Gilead Sciences, personal fees from Janssen-Cilag, grants and personal fees from Roche, personal fees from Merck, MSD, personal fees from Biogen, personal fees from Falk Foundation, personal fees from Siemens, outside the submitted work. Michael P. Manns has received Study support, grants, consulting fees, lecture fees and travel support from Bristol Myers Squibb, Gilead, Merck, Janssen and Abbvie. The other authors report no conflicts of interest.

Additional information

Funding

This study was sponsored by a Clinical Leave stipend for the last author by the German Center for Infection Research (DZIF) and was supported by iMed, the Helmholtz Association’s Initiative on Personalized Medicine.