益生菌、利福昔明和乳果糖治疗轻微肝性脑病及肠道微生物群的效果比较

Comparison of the effects of probiotics, rifaximin, and lactulose in the treatment of minimal hepatic encephalopathy and gut microbiota.

作者信息

Wang Ming-Wei, Ma Wei-Juan, Wang Yan, Ma Xiao-Han, Xue Yu-Feng, Guan Jing, Chen Xi

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Anhui Provincial Key Laboratory of Digestive Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

出版信息

Front Microbiol. 2023 Mar 24;14:1091167. doi: 10.3389/fmicb.2023.1091167. eCollection 2023.

DOI:10.3389/fmicb.2023.1091167

PMID:37032856

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10080009/

Abstract

BACKGROUND

Minimal hepatic encephalopathy (MHE) is an early stage in the pathogenesis of hepatic encephalopathy. Intestinal microbiota is involved in the pathogenesis of hepatic encephalopathy and has become an important therapeutic target. Since there is no unified treatment principle for MHE, this study was conducted to determine the safety and efficacy of different intestinal microecological modulators in the treatment of MHE, and to explore the potential mechanism through intestinal microbiota analysis.

METHODS

Patients with liver cirrhosis were screened for MHE using psychometric hepatic encephalopathy score test. Patients diagnosed with MHE were enrolled and received probiotics, rifaximin, or lactulose for 4 weeks. Adverse events were recorded. The psychometric hepatic encephalopathy score test was performed after treatment. Samples of blood and stool were collected at entry and 4 weeks. Blood samples were analyzed to assess blood ammonia, liver, kidney, and hemostatic functions. Stool microbiota were sequenced to confirm changes in microbial composition.

RESULTS

Of 323 patients with liver cirrhosis, 74 patients were diagnosed with MHE. In all, 54 patients were enrolled and 52 who agree to follow-up were included in analysis. The recovery rates of MHE patients received probiotics, rifaximin, and lactulose were 58.8% (20/34), 45.5% (5/11), and 57.1% (4/7), respectively. Probiotics and rifaximin improved liver function in MHE patients to a certain extent. Taxonomic compositions of gut microbiota in MHE patients were distinct from healthy people before treatment; the differences were significantly reduced after treatment, and the gut microbiota gradually resembled the structure of healthy individuals. We found that the relative abundance of specific taxa associated with anti-inflammatory and good cognitive functions was increased in MHE patients after treatment. Accordingly, metabolic pathways in MHE patients were altered before and after treatment. Downregulated pathways after probiotics treatment included glycometabolism and degradation of aromatic compounds. After lactulose treatment, degradation pathways of arginine and ornithine showed a downward trend.

CONCLUSION

Probiotics, rifaximin, and lactulose are safe and effective in the treatment of MHE, and improve the composition of gut microbiota to some extent.

摘要

背景

轻微肝性脑病（MHE）是肝性脑病发病机制的早期阶段。肠道微生物群参与肝性脑病的发病机制，已成为重要的治疗靶点。由于MHE尚无统一的治疗原则，本研究旨在确定不同肠道微生态调节剂治疗MHE的安全性和有效性，并通过肠道微生物群分析探索潜在机制。

方法

采用心理测量肝性脑病评分测试对肝硬化患者进行MHE筛查。将诊断为MHE的患者纳入研究，给予益生菌、利福昔明或乳果糖治疗4周。记录不良事件。治疗后进行心理测量肝性脑病评分测试。在入组时和4周时采集血液和粪便样本。分析血液样本以评估血氨、肝、肾和止血功能。对粪便微生物群进行测序以确认微生物组成的变化。

结果

在323例肝硬化患者中，74例被诊断为MHE。共有54例患者入组，52例同意随访的患者纳入分析。接受益生菌、利福昔明和乳果糖治疗的MHE患者的恢复率分别为58.8%（20/34）、45.5%（5/11）和57.1%（4/7）。益生菌和利福昔明在一定程度上改善了MHE患者的肝功能。治疗前，MHE患者肠道微生物群的分类组成与健康人不同；治疗后差异显著降低，肠道微生物群逐渐类似于健康个体的结构。我们发现，治疗后MHE患者中与抗炎和良好认知功能相关的特定分类群的相对丰度增加。因此，MHE患者治疗前后的代谢途径发生了改变。益生菌治疗后下调的途径包括糖代谢和芳香族化合物降解。乳果糖治疗后，精氨酸和鸟氨酸的降解途径呈下降趋势。