Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond, Virginia, USA
Microbiome Analysis Center, George Mason University, Manassas, Virginia, USA.
Gut. 2021 Jun;70(6):1162-1173. doi: 10.1136/gutjnl-2020-322470. Epub 2020 Sep 30.
Altered bacterial composition is associated with disease progression in cirrhosis but the role of virome, especially phages, is unclear.
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.
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. and 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 and Myoviridae. Pre/post: No changes in alpha/beta diversity of phages or bacteria were seen postrifaximin. Phage-bacterial linkages centred around urease-producing species collapsed postrifaximin.
Unlike bacteria, faecal phages are sparsely linked with cirrhosis characteristics and 90-day outcomes. Phage and bacterial linkages centred on urease-producing, ammonia-generating species were affected by disease progression and rifaximin therapy and were altered in patients who experienced 90-day hospitalisations.
细菌组成的改变与肝硬化的疾病进展有关，但病毒组，特别是噬菌体的作用尚不清楚。
纳入了横断面和利福昔明前后队列。横断面：纳入了对照组和肝硬化门诊患者（代偿期，服用乳果糖（Cirr-L），服用利福昔明（Cirr-LR）），并随访 90 天住院情况。利福昔明前后：代偿期肝硬化患者在服用利福昔明 8 周前后采集粪便。分析对照组与肝硬化、肝硬化患者中、住院与非住院、利福昔明前后的细菌和噬菌体及其相关网络。
横断面：纳入了 40 名对照组和 163 名肝硬化患者（63 名代偿期，43 名 Cirr-L，57 名 Cirr-LR）。Cirr-L/LR 两组在终末期肝病模型（MELD）评分上相似，但 Cirr-L 组的住院率高于 Cirr-LR 组（56% vs 30%，p=0.008）。细菌的 alpha 和 beta 多样性从对照组到 Cirr-LR 逐渐恶化。虽然噬菌体的 alpha 多样性相似，但各组之间的 beta 多样性不同。定植菌与 MELD 呈负相关，机会致病菌与 MELD 呈正相关，但只有中等程度的噬菌体-MELD 相关性。在对照组中，噬菌体-细菌相关网络的复杂性最高，Cirr-L 最低，Cirr-LR 增加。Cirr-LR 患者中，噬菌体与定植菌相关，而 Cirr-L 住院患者中，机会致病菌更多，共生菌和噬菌体减少，并且集中于和肌尾噬菌体科。利福昔明前后：利福昔明后，噬菌体或细菌的 alpha 和 beta 多样性没有变化。利福昔明后，以产脲酶的 种为中心的噬菌体-细菌联系崩溃。
与细菌不同，粪便噬菌体与肝硬化特征和 90 天预后的相关性较差。以产脲酶、产氨的 种为中心的噬菌体和细菌联系受疾病进展和利福昔明治疗的影响，在发生 90 天住院的患者中发生改变。
