Influence of proton pump inhibitors on microbiota in chronic liver disease patients

  • Kenta Yamamoto
  • Masatoshi IshigamiEmail author
  • Takashi Honda
  • Tomoaki Takeyama
  • Takanori Ito
  • Yoji Ishizu
  • Teiji Kuzuya
  • Kazuhiko Hayashi
  • Hidemi Goto
  • Yoshiki Hirooka
Original Article



Current knowledge suggests that proton pump inhibitors (PPIs) are associated with an increased risk of hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP). These conditions and PPI use are related to gut microbiota. The aim of this study is to research the changes in gut microbiota caused by PPI in patients with chronic liver disease.


From 198 Japanese patients, 31 patients in the PPI and non-PPI groups were matched using propensity score matching (PSM) based on age, sex, and Child–Turcotte–Pugh class. We investigated the gut microbial composition of stool samples using the Illumina MiSeq sequencing platform and compared them using linear discriminant analysis effect size and phylogenetic investigation of communities by reconstruction of unobserved states.


Before PSM, Child–Turcotte–Pugh score (p = 0.038), ascites (p = 0.049), encephalopathy (p = 0.023), and esophageal varices (p < 0.01) were significantly higher in the PPI group than in the non-PPI group. After PSM, six genera, consisting of Lactobacillus, Streptococcus, Selenomonas, Veillonella, Campylobacter, and Haemophilus were enriched in the PPI group. Eggerthella, Paraprevotella, Turicibacter, Dorea, Anaerotruncus, and Ruminococcus were less abundant in the PPI group. We identified five types of level 3 KEGG pathways predicted to be significantly different.


Part of microbial changes caused by PPI use was common to the changes by progression of liver cirrhosis. Increases in oral bacterial flora and decreases in autochthonous flora may produce the intestinal environment which tends to make the risk factor for HE or SBP.


Microbiota Proton pump inhibitor Liver Next generation sequencing Propensity score matching methods 



We thank Ms. Akina Ooishi at Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine for technical assistance to DNA isolate and 16S rRNA gene sequence.

Compliance with ethical standards

Ethical approval

This study was approved by the Research Ethics Committee of Nagoya University Hospital on August 30, 2016 (Protocol number 2015-0420). In accordance with the Declaration of Helsinki, written informed consent was obtained from all patients before registration. This study is registered in University Hospital Medical Information Network Clinical Trials Registry (UMIN ID: 000020269).

Supplementary material

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Supplementary material 1 (PDF 28 kb)
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Supplementary material 5 (PDF 1293 kb)


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Copyright information

© Asian Pacific Association for the Study of the Liver 2019

Authors and Affiliations

  • Kenta Yamamoto
    • 1
  • Masatoshi Ishigami
    • 1
    Email author
  • Takashi Honda
    • 1
  • Tomoaki Takeyama
    • 1
  • Takanori Ito
    • 1
  • Yoji Ishizu
    • 1
  • Teiji Kuzuya
    • 1
  • Kazuhiko Hayashi
    • 1
  • Hidemi Goto
    • 1
  • Yoshiki Hirooka
    • 1
  1. 1.Department of Gastroenterology and HepatologyNagoya University Graduate School of MedicineNagoyaJapan

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