Bajaj Jasmohan S, Heuman Douglas M, Hylemon Phillip B, Sanyal Arun J, White Melanie B, Monteith Pamela, Noble Nicole A, Unser Ariel B, Daita Kalyani, Fisher Andmorgan R, Sikaroodi Masoumeh, Gillevet Patrick M
Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, United States.
Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, United States.
J Hepatol. 2014 May;60(5):940-7. doi: 10.1016/j.jhep.2013.12.019. Epub 2013 Dec 25.
BACKGROUND & AIMS: The gut microbiome is altered in cirrhosis; however its evolution with disease progression is only partly understood. We aimed to study changes in the microbiome over cirrhosis severity, its stability over time and its longitudinal alterations with decompensation.
Controls and age-matched cirrhotics (compensated/decompensated/hospitalized) were included. Their stool microbiota was quantified using multi-tagged pyrosequencing. The ratio of autochthonous to non-autochthonous taxa was calculated as the cirrhosis dysbiosis ratio (CDR); a low number indicating dysbiosis. Firstly, the microbiome was compared between controls and cirrhotic sub-groups. Secondly, for stability assessment, stool collected twice within 6months in compensated outpatients was analyzed. Thirdly, changes after decompensation were assessed using (a) longitudinal comparison in patients before/after hepatic encephalopathy development (HE), (b) longitudinal cohort of hospitalized infected cirrhotics MELD-matched to uninfected cirrhotics followed for 30days.
244 subjects [219 cirrhotics (121 compensated outpatients, 54 decompensated outpatients, 44 inpatients) and 25 age-matched controls] were included. CDR was highest in controls (2.05) followed by compensated (0.89), decompensated (0.66), and inpatients (0.32, p<0.0001) and negatively correlated with endotoxin. Microbiota and CDR remained unchanged in stable outpatient cirrhotics (0.91 vs. 0.86, p=0.45). In patients studied before/after HE development, dysbiosis occurred post-HE (CDR: 1.2 to 0.42, p=0.03). In the longitudinal matched-cohort, microbiota were significantly different between infected/uninfected cirrhotics at baseline and a low CDR was associated with death and organ failures within 30days.
Progressive changes in the gut microbiome accompany cirrhosis and become more severe in the setting of decompensation. The cirrhosis dysbiosis ratio may be a useful quantitative index to describe microbiome alterations accompanying cirrhosis progression.
肝硬化患者的肠道微生物群会发生改变；然而，人们对其随疾病进展的演变情况仅了解一部分。我们旨在研究微生物群在肝硬化严重程度方面的变化、其随时间的稳定性以及失代偿时的纵向改变。
纳入对照组以及年龄匹配的肝硬化患者（代偿期/失代偿期/住院患者）。使用多标签焦磷酸测序法定量分析他们的粪便微生物群。计算本地菌群与非本地菌群的比例作为肝硬化失调率（CDR）；该数值较低表明存在失调。首先，比较对照组与肝硬化亚组之间的微生物群。其次，为进行稳定性评估，分析代偿期门诊患者在6个月内两次采集的粪便。第三，使用以下方法评估失代偿后的变化：（a）对肝性脑病（HE）发生前后的患者进行纵向比较，（b）对住院的感染性肝硬化患者与未感染的肝硬化患者进行MELD匹配的纵向队列研究，随访30天。
纳入244名受试者[219名肝硬化患者（121名代偿期门诊患者、54名失代偿期门诊患者、44名住院患者）和25名年龄匹配的对照组]。CDR在对照组中最高（2.05），其次是代偿期患者（0.89）、失代偿期患者（0.66）和住院患者（0.32，p<0.0001），且与内毒素呈负相关。稳定的门诊肝硬化患者的微生物群和CDR保持不变（0.91对0.86，p=0.45）。在对HE发生前后进行研究的患者中，失调发生在HE之后（CDR：1.2至0.42，p=0.03）。在纵向匹配队列中，感染/未感染的肝硬化患者在基线时微生物群存在显著差异，低CDR与30天内的死亡和器官衰竭相关。
肠道微生物群的渐进性变化伴随肝硬化发生，并在失代偿情况下变得更加严重。肝硬化失调率可能是描述肝硬化进展过程中微生物群改变的有用定量指标。
