RT Journal Article SR Electronic T1 Interaction of bacterial metagenome and virome in patients with cirrhosis and hepatic encephalopathy JF Gut JO Gut FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP 1162 OP 1173 DO 10.1136/gutjnl-2020-322470 VO 70 IS 6 A1 Bajaj, Jasmohan S A1 Sikaroodi, Masoumeh A1 Shamsaddini, Amirhossein A1 Henseler, Zachariah A1 Santiago-Rodriguez, Tasha A1 Acharya, Chathur A1 Fagan, Andrew A1 Hylemon, Phillip B A1 Fuchs, Michael A1 Gavis, Edith A1 Ward, Tonya A1 Knights, Dan A1 Gillevet, Patrick M YR 2021 UL http://gut.bmj.com/content/70/6/1162.abstract AB 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.Data are presented in supplement to the extent allowed by our institutional review boards