Subjects

Objectives

Cirrhosis is associated with gut microbial dysbiosis, high readmissions and proton pump inhibitor (PPI) overuse, which could be inter-linked. Our aim was to determine the effect of PPI use, initiation and withdrawl on gut microbiota and readmissions in cirrhosis.

Methods

Four cohorts were enrolled. Readmissions study: Cirrhotic inpatients were followed throughout the hospitalization and 30/90-days post-discharge. PPI initiation, withdrawal/continuation patterns were analyzed between those with/without readmissions. Cross-sectional microbiota study: Cirrhotic outpatients and controls underwent stool microbiota analysis. Beneficial autochthonous and oral-origin taxa analysis vis-à-vis PPI use was performed. Longitudinal studies: Two cohorts of decompensated cirrhotic outpatients were enrolled. Patients on chronic unindicated PPI use were withdrawn for 14 days. Patients not on PPI were started on omeprazole for 14 days. Microbial analysis for oral-origin taxa was performed pre/post-intervention.

Results

Readmissions study: 343 inpatients (151 on admission PPI) were enrolled. 21 were withdrawn and 45 were initiated on PPI resulting in a PPI use increase of 21%. PPIs were associated with higher 30 (p = 0.002) and 90-day readmissions (p = 0.008) independent of comorbidities, medications, MELD and age. Cross-sectional microbiota: 137 cirrhotics (59 on PPI) and 45 controls (17 on PPI) were included. PPI users regardless of cirrhosis had higher oral-origin microbiota while cirrhotics on PPI had lower autochthonous taxa compared to the rest. Longitudinal studies: Fifteen decompensated cirrhotics tolerated omeprazole initiation with an increase in oral-origin microbial taxa compared to baseline. PPIs were withdrawn from an additional 15 outpatients, which resulted in a significant reduction of oral-origin taxa compared to baseline.

Conclusions

PPIs modulate readmission risk and microbiota composition in cirrhosis, which responds to withdrawal. The systematic withdrawal and judicious use of PPIs is needed from a clinical and microbiological perspective in decompensated cirrhosis.

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Author information

Affiliations

  1. Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA

    • Jasmohan S Bajaj MD
    • , Chathur Acharya MD
    • , Andrew Fagan BS
    • , Melanie B White RN
    • , Edith Gavis RN
    • , Douglas M Heuman MD
    • , Michael Fuchs MD
    • , Puneet Puri MD
    • , Mitchell L Schubert MD
    • , Arun J Sanyal MD
    • , Richard K Sterling MD
    • , R Todd Stravitz MD
    • , Mohammad S Siddiqui MD
    • , Velimir Luketic MD
    •  & Hannah Lee MD
  2. Microbiology, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA

    • Phillip B Hylemon PhD
  3. Microbiome Analysis Center, George Mason University, Manassas, VA, USA

    • Masoumeh Sikaroodi PhD
    •  & Patrick M Gillevet PhD

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Guarantor of the article

JSB is the guarantor.

Specific author contributions

JSB conceptualized the study, MS and PMG were involved in microbiota analysis, PBH was involved in the critical revisions, CA, MBW, AF, and EAG were involved in research coordination, Rest of the authors were involved in subject recruitment and follow-up.

Financial support

This work was partly supported from American College of Gastroenterology Clinical Research Award, VA Merit Review I0CX001076, McGuire Research Institute and an investigator-initiated grant by Grifols Pharmaceuticals, all to JSB. None of the study sponsors had any role in the study design, collection, analysis, and interpretation of the data and in the writing of the report.

Potential competing interests

None.

Corresponding author

Correspondence to Jasmohan S Bajaj MD.

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DOI

https://doi.org/10.1038/s41395-018-0085-9