IDENTIFICATION OF NOVEL INTESTINAL MICROBIOTA-BASED MARKERS ASSOCIATED WITH DYSBIOSIS, SEPSIS AND SHORT-TERM MORTALITY IN ALCOHOL-RELATED DECOMPENSATED CIRRHOSIS AND ACUTE-ON-CHRONIC LIVER FAILURE

IF 4.4 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology Pub Date : 2025-09-01 DOI:10.1016/j.aohep.2025.101972

María Daniela Sánchez Gutiérrez , Paula Alejandra Castaño Jimenéz , Luis Gilberto Huerta Gómez , Marina Campos Valdez , Miriam Ruth Bueno Topete , Tonatiuh Abimael Baltazar Díaz

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引用次数: 0

Abstract

Introduction and Objectives

Decompensated cirrhosis (DC) and acute-on-chronic liver failure (ACLF) related to alcohol present high morbidity and mortality and complications such as sepsis and multiorgan failure. The intestinal microbiota (IM) suffers from marked dysbiosis, altering SCFA biosynthesis and affecting the gut-liver axis. The microbial pathways involved, poorly understood in these pathologies, could represent useful prognostic markers.

To evaluate the relative quantification of bacterial SCFA genes in the IM of patients with CD and ACLF, and their association with different clinical outcomes and alpha-diversity.

Materials and Methods

Retrospective analytical study. Fecal samples from 19 ACLF patients, 16 DC, and 16 healthy controls (HC) were included. The butCoA, buk, ackA, and mmdA genes were quantified by qPCR. ROC curves and Kaplan-Meier analyses were performed using GraphPad. Approval number: CI-01023. No conflicts of interest are reported.

Results

Relative abundances of butCoA and ackA genes were significantly decreased in DC and ACLF patients (p<0.05), whereas mmdA increased in DC. buk increased in patients who died at 28 days (p<0.01) and showed a negative correlation with alpha-diversity, being associated with dysbiosis. Furthermore, buk and butCoA discriminated 28-day mortality in DC and ACLF (AUROC 0.75 and 0.85, respectively). In Kaplan-Meier analyses, increased buk was associated with 28-day mortality of 53% in DC and 71% in ACLF.

Conclusions

Intestinal microbiota of DC/ACLF showed reduction of butCoA, ackA, and mmdA, correlating with functional loss. Increased buk was associated with 28-day mortality, loss of alpha-diversity and sepsis. These findings propose novel microbial biomarkers in the Mexican population which will have to be validated later.

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鉴定与酒精相关失代偿性肝硬化和急性慢性肝衰竭中生态失调、败血症和短期死亡率相关的新型肠道微生物群标志物

与酒精相关的失代偿性肝硬化（DC）和急性慢性肝衰竭（ACLF）具有很高的发病率和死亡率以及脓毒症和多器官衰竭等并发症。肠道微生物群（IM）遭受明显的生态失调，改变SCFA生物合成并影响肠-肝轴。所涉及的微生物途径，在这些病理中知之甚少，可以代表有用的预后标记。评估CD和ACLF患者IM中细菌SCFA基因的相对定量，以及它们与不同临床结局和α -多样性的关系。材料与方法回顾性分析研究。纳入了19例ACLF患者、16例DC和16例健康对照（HC）的粪便样本。采用qPCR法对bucoa、buk、ackA和mmdA基因进行定量分析。使用GraphPad进行ROC曲线和Kaplan-Meier分析。批准文号：CI-01023。无利益冲突报告。结果DC和ACLF患者的butCoA和ackA基因相对丰度显著降低（p < 0.05），而DC患者的mmdA相对丰度升高。Buk在28天死亡的患者中升高（p<0.01），并与α -多样性呈负相关，与生态失调有关。此外，buk和butCoA区分DC和ACLF的28天死亡率（AUROC分别为0.75和0.85）。Kaplan-Meier分析显示，体重增加与DC患者28天死亡率相关，分别为53%和71%。结论DC/ACLF患者肠道菌群中bucoa、ackA和mmdA的减少与功能丧失相关。buk增加与28天死亡率、α -多样性丧失和败血症有关。这些发现在墨西哥人群中提出了新的微生物生物标志物，这将在以后得到验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of hepatology 医学-胃肠肝病学

CiteScore

7.90

自引率

2.60%

发文量

183

审稿时长

4-8 weeks

期刊介绍： Annals of Hepatology publishes original research on the biology and diseases of the liver in both humans and experimental models. Contributions may be submitted as regular articles. The journal also publishes concise reviews of both basic and clinical topics.