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Abstract Details
Interaction of bacterial metagenome and virome in patients with cirrhosis and hepatic encephalopathy
Jasmohan S Bajaj1, Masoumeh Sikaroodi2, Amirhossein Shamsaddini2, Zachariah Henseler3, Tasha Santiago-Rodriguez3, Chathur Acharya4, Andrew Fagan4, Phillip B Hylemon4, Michael Fuchs4, Edith Gavis4, Tonya Ward3, Dan Knights356, Patrick M Gillevet2
Author information
1Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond, Virginia, USA jasmohan@gmail.com.
2Microbiome Analysis Center, George Mason University, Manassas, Virginia, USA.
3Diversigen, New Brighton, Minnesota, USA.
4Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond, Virginia, USA.
5Department of Computer Science and Engineering, U, University of Minnesota, Minneapolis, MN, USA.
6Minnesota Biotechnology Institute, University of Minnesota, Minneapolis, MN, USA.
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. Microviridae and Faecalibacterium phages were linked with autochthonous bacteria in Cirr-LR, but not Cirr-L hospitalised patients had greater pathobionts, lower commensal bacteria and phages focused on Streptococcus, Lactococcus and Myoviridae. Pre/post: No changes in alpha/beta diversity of phages or bacteria were seen postrifaximin. Phage-bacterial linkages centred around urease-producing Streptococcus species collapsed postrifaximin.
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 Streptococcus species were affected by disease progression and rifaximin therapy and were altered in patients who experienced 90-day hospitalisations.