Interaction of bacterial metagenome and virome in patients with cirrhosis and hepatic encephalopathy
© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:70 |
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| Enthalten in: |
Gut - 70(2021), 6 vom: 30. Juni, Seite 1162-1173 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bajaj, Jasmohan S [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.01.2022 Date Revised 11.01.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1136/gutjnl-2020-322470 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM315693762 |
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| 100 | 1 | |a Bajaj, Jasmohan S |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Interaction of bacterial metagenome and virome in patients with cirrhosis and hepatic encephalopathy |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 11.01.2022 | ||
| 500 | |a Date Revised 11.01.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a OBJECTIVE: Altered bacterial composition is associated with disease progression in cirrhosis but the role of virome, especially phages, is unclear | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a cirrhosis | |
| 650 | 4 | |a hepatic encephalopathy | |
| 650 | 4 | |a intestinal microbiology | |
| 650 | 4 | |a liver | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Gastrointestinal Agents |2 NLM | |
| 650 | 7 | |a Lactulose |2 NLM | |
| 650 | 7 | |a 4618-18-2 |2 NLM | |
| 650 | 7 | |a Rifaximin |2 NLM | |
| 650 | 7 | |a L36O5T016N |2 NLM | |
| 700 | 1 | |a Sikaroodi, Masoumeh |e verfasserin |4 aut | |
| 700 | 1 | |a Shamsaddini, Amirhossein |e verfasserin |4 aut | |
| 700 | 1 | |a Henseler, Zachariah |e verfasserin |4 aut | |
| 700 | 1 | |a Santiago-Rodriguez, Tasha |e verfasserin |4 aut | |
| 700 | 1 | |a Acharya, Chathur |e verfasserin |4 aut | |
| 700 | 1 | |a Fagan, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Hylemon, Phillip B |e verfasserin |4 aut | |
| 700 | 1 | |a Fuchs, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Gavis, Edith |e verfasserin |4 aut | |
| 700 | 1 | |a Ward, Tonya |e verfasserin |4 aut | |
| 700 | 1 | |a Knights, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Gillevet, Patrick M |e verfasserin |4 aut | |
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