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

Abstract

ObjectiveAltered bacterial composition is associated with disease progression in cirrhosis but the role of virome, especially phages, is unclear.DesignCross-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.ResultsCross-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.ConclusionUnlike 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.

The Gut-Liver Axis in Cholestatic Liver Diseases

“…The virome has only been investigated in NAFLD, alcoholic hepatitis, and cirrhotic patients [ 300 , 301 , 302 ]. In NAFLD, 420 different viral species were detected in all patients, but only 19 of them were found in at least 50% of all fecal samples.…”

“…Fecal VLPs showed higher diversity in patients with alcoholic hepatitis and alterations of certain taxa ( Staphylococcus phages, Herpesviridae ) could be correlated with disease severity and mortality [ 301 ]. In cirrhotic patients on the other hand the link between fecal phages and cirrhosis specifications and 90-day outcome was modest [ 302 ]. The virome was not only investigated in feces, but also from plasma.…”

Dysbiotic oral and gut viromes in untreated and treated rheumatoid arthritis patients

“…Close interactions of gut virome and bacterial microbiome had been reported in patients of several diseases such as inflammatory bowel disease (IBD)[17, 47] and cirrhosis[48]. Here, we enriched their relationships in the oral ecosystem by constructing the virus-bacteria co-abundance networks in both dental plaque and saliva samples.…”

Case–control study: Proton pump inhibitor use is a major risk factor for hepatic encephalopathy after TIPS

“…28,29 PPIs are known to have significant effects on the gut microbiome, [30][31][32] which may stimulate the production of toxic metabolites that precipitate hepatic encephalopathy. 33 Since the majority of the patients had TIPS for ascites, this group may be most vulnerable to changes of the intestinal microbiome which PPI use may contribute to.…”