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Bajaj JS, Sikaroodi M, Shamsaddini A, et al. Interaction of bacterial metagenome and virome in patients with cirrhosis and hepatic encephalopathy. Gut. 2020;70(6):1162-1173doi: 10.1136/gutjnl-2020-322470.
Bajaj, J. S., Sikaroodi, M., Shamsaddini, A., Henseler, Z., Santiago-Rodriguez, T., Acharya, C., Fagan, A., Hylemon, P. B., Fuchs, M., Gavis, E., Ward, T., Knights, D., & Gillevet, P. M. (2021). Interaction of bacterial metagenome and virome in patients with cirrhosis and hepatic encephalopathy. Gut, 70(6), 1162-1173. https://doi.org/10.1136/gutjnl-2020-322470
Bajaj, Jasmohan S, et al. "Interaction of bacterial metagenome and virome in patients with cirrhosis and hepatic encephalopathy." Gut vol. 70,6 (2021): 1162-1173. doi: https://doi.org/10.1136/gutjnl-2020-322470
Bajaj JS, Sikaroodi M, Shamsaddini A, Henseler Z, Santiago-Rodriguez T, Acharya C, Fagan A, Hylemon PB, Fuchs M, Gavis E, Ward T, Knights D, Gillevet PM. Interaction of bacterial metagenome and virome in patients with cirrhosis and hepatic encephalopathy. Gut. 2021 Jun;70(6):1162-1173. doi: 10.1136/gutjnl-2020-322470. Epub 2020 Sep 30. PMID: 32998876.
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Gut. 2021 Jun;70(6):1162-1173. doi: 10.1136/gutjnl-2020-322470. Epub 2020 Sep 30.

Interaction of bacterial metagenome and virome in patients with cirrhosis and hepatic encephalopathy.

Gut

Jasmohan S Bajaj, Masoumeh Sikaroodi, Amirhossein Shamsaddini, Zachariah Henseler, Tasha Santiago-Rodriguez, Chathur Acharya, Andrew Fagan, Phillip B Hylemon, Michael Fuchs, Edith Gavis, Tonya Ward, Dan Knights, Patrick M Gillevet

Affiliations

  1. Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond, Virginia, USA [email protected].
  2. Microbiome Analysis Center, George Mason University, Manassas, Virginia, USA.
  3. Diversigen, New Brighton, Minnesota, USA.
  4. Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond, Virginia, USA.
  5. Department of Computer Science and Engineering, U, University of Minnesota, Minneapolis, MN, USA.
  6. Minnesota Biotechnology Institute, University of Minnesota, Minneapolis, MN, USA.

PMID: 32998876 DOI: 10.1136/gutjnl-2020-322470

Abstract

OBJECTIVE: Altered bacterial composition is associated with disease progression in cirrhosis but the role of virome, especially phages, is unclear.

DESIGN: Cross-sectional and pre/post rifaximin cohorts were enrolled. Cross-sectional: controls and cirrhotic outpatients (compensated, on lactulose (Cirr-L), on rifaximin (Cirr-LR)) were included and followed for 90-day hospitalisations. Pre/post: compensated cirrhotics underwent stool collection pre/post 8 weeks of rifaximin. Stool metagenomics for bacteria and phages and their correlation networks were analysed in controls versus cirrhosis, within cirrhotics, hospitalised/not and pre/post rifaximin.

RESULTS: Cross-sectional: 40 controls and 163 cirrhotics (63 compensated, 43 Cirr-L, 57 Cirr-LR) were enrolled. Cirr-L/LR groups were similar on model for end-stage liver disease (MELD) score but Cirr-L developed greater hospitalisations versus Cirr-LR (56% vs 30%, p=0.008). Bacterial alpha/beta diversity worsened from controls through Cirr-LR. While phage alpha diversity was similar, beta diversity was different between groups. Autochthonous bacteria linked negatively, pathobionts linked positively with MELD but only modest phage-MELD correlations were seen. Phage-bacterial correlation network complexity was highest in controls, lowest in Cirr-L and increased in Cirr-LR.

CONCLUSION: Unlike bacteria, faecal phages are sparsely linked with cirrhosis characteristics and 90-day outcomes. Phage and bacterial linkages centred on urease-producing, ammonia-generating

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Keywords: cirrhosis; hepatic encephalopathy; intestinal microbiology; liver

Conflict of interest statement

Competing interests: DK, EH, TSR and TW are employees of Diversigen, where the metagnomic and virome analysis was performed.

Publication Types

Grant support