Philips Cyriac Abby, Augustine Philip, Ganesan Karthik, Ranade Shatakshi, Chopra Varun, Patil Kunal, Shende Sonie, Ahamed Rizwan, Kumbar Sandeep, Rajesh Sasidharan, George Tom, Mohanan Meera, Mohan Narain, Phadke Nikhil, Rani Mridula, Narayanan Arjun, Jagan Suchetha M
The Liver Unit and Monarch Liver Lab, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi, 682 028, India.
Philip Augustine Associates (P) Ltd, Ernakulam Medical Center, Room no: 3. Ground Floor, Kochi, 682 028, India.
Indian J Gastroenterol. 2022 Feb;41(1):37-51. doi: 10.1007/s12664-021-01157-9. Epub 2022 Jan 6.
Dysbiotic gut bacteria engage in the development and progression of severe alcoholic hepatitis (SAH). We aimed to characterize bacterial communities associated with clinical events (CE), identify significant bacteria linked to CE, and define bacterial relationships associated with specific CE and outcomes at baseline and after treatment in SAH.
We performed 16-s rRNA sequencing on stool samples (n=38) collected at admission and the last follow-up within 90 days in SAH patients (n=26; 12 corticosteroids; 14 granulocyte colony-stimulating factor, [G-CSF]). Validated pipelines were used to plot bacterial communities, profile functional metabolism, and identify significant taxa and functional metabolites. Conet/NetworkX® was utilized to identify significant non-random patterns of bacterial co-presence and mutual exclusion for clinical events.
All the patients were males with median discriminant function (DF) 64, Child-Turcotte-Pugh (CTP) 12, and model for end-stage liver disease (MELD) score 25.5. At admission, 27%, 42%, and 58% had acute kidney injury (AKI), hepatic encephalopathy (HE), and infections respectively; 38.5% died at end of follow-up. Specific bacterial families were associated with HE, sepsis, disease severity, and death. Lachnobacterium and Catenibacterium were associated with HE, and Pediococcus with death after steroid treatment. Change from Enterococcus (promotes AH) to Barnesiella (inhibits E. faecium) was significant after G-CSF. Phenylpropanoid-biosynthesis (innate-immunity) and glycerophospholipid-metabolism (cellular-integrity) pathways in those without infections and the death, respectively, were upregulated. Mutual interactions between Enterococcus cecorum, Acinetobacter schindleri, and Mitsuokella correlated with admission AKI.
Specific gut microbiota, their interactions, and metabolites are associated with complications of SAH and treatment outcomes. Microbiota-based precision medicine as adjuvant treatment may be a new therapeutic area.
肠道菌群失调与严重酒精性肝炎（SAH）的发生和发展有关。我们旨在描述与临床事件（CE）相关的细菌群落，确定与CE相关的重要细菌，并确定在SAH患者基线期及治疗后与特定CE和预后相关的细菌关系。
我们对SAH患者（n = 26；12例接受皮质类固醇治疗；14例接受粒细胞集落刺激因子[G-CSF]治疗）入院时和90天内最后一次随访时采集的粪便样本（n = 38）进行了16-s rRNA测序。使用经过验证的流程来绘制细菌群落、分析功能代谢，并识别重要的分类群和功能代谢物。利用Conet/NetworkX®识别临床事件中细菌共存和相互排斥的重要非随机模式。
所有患者均为男性，判别功能（DF）中位数为64，Child-Turcotte-Pugh（CTP）评分为12，终末期肝病模型（MELD）评分为25.5。入院时，分别有27%、42%和58%的患者发生急性肾损伤（AKI）、肝性脑病（HE）和感染；38.5%的患者在随访结束时死亡。特定细菌家族与HE、败血症、疾病严重程度和死亡相关。乳酸杆菌属和链状杆菌属与HE相关，片球菌属与类固醇治疗后的死亡相关。使用G-CSF后，从促进AH的肠球菌转变为抑制粪肠球菌的巴涅西氏菌属的变化显著。在未发生感染和死亡的患者中，苯丙烷生物合成（先天免疫）和甘油磷脂代谢（细胞完整性）途径分别上调。盲肠肠球菌、辛德瑞拉不动杆菌和米氏菌之间的相互作用与入院时的AKI相关。
特定的肠道微生物群、它们的相互作用和代谢物与SAH的并发症和治疗结果相关。基于微生物群的精准医学作为辅助治疗可能是一个新的治疗领域。
