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乙型肝炎所致肝硬化患者肠道微生物群失调与胆汁酸之间的关系

Relationship between gut microbiota dysbiosis and bile acid in patients with hepatitis B-induced cirrhosis.

作者信息

Li Yannan, Zhang Dan, Tian Tian, Xie Jing, Wang Xiaolin, Deng Wenjun, Hao Ningbo, Li Changzheng

机构信息

The Postgraduate Training Base of Jinzhou Medical University (Characteristic Medical Center of the PLA Rocket Force), Beijing, China.

Department of Gastroenterology, Daqing Oilfield General Hospital, Heilongjiang, China.

出版信息

BMC Gastroenterol. 2025 Aug 4;25(1):552. doi: 10.1186/s12876-025-04159-5.

DOI:10.1186/s12876-025-04159-5
PMID:40760429
Abstract

BACKGROUND

Dysbiosis of the gut microbiota is a significant factor influencing the progression of hepatitis B-related cirrhosis (HBC). Bile acid (BA) metabolism is increasingly recognized as a key participant in the liver-gut microbiota axis.

METHODS

A total of 46 patients with HBC and 33 healthy adults were enrolled in this study. The HBC patients were divided into a BA-normal group and a BA-high group. Fecal samples were collected from patients under the conditions of their daily diet, and the 16 S rRNA test was performed for each sample.

RESULTS

Compared with that in healthy adults, the alpha diversity of the gut microbiota in HBC patients significantly changed, with a decrease in beneficial microbiota and an increase in opportunistic pathogens. Notably, Bacilli, Enterobacteriales, Streptococcaceae, Veillonella and Lactobacillales were significantly increased in BA-high patients, whereas Clostridia and Clostridiales were significantly decreased. Akkermansiaceae abundance was reduced in the HBC group, and Lactobacillales was markedly enriched in HBC patients, with its abundance proportionally increasing with increasing BA.

CONCLUSION

These findings provide critical insights for investigating the gut microbiota‒BA crosstalk in HBC, facilitating the discovery of novel biomarkers for disease monitoring and the development of microbiota-targeted therapeutic strategies modulating BA metabolism to intervene in HBC progression.

TRIAL REGISTRATION

This study was registered in the Chinese Clinical Trial Registry (ChiCTR2400090990) on October 17, 2024 (retrospectively registered).

摘要

背景

肠道微生物群失调是影响乙型肝炎相关肝硬化(HBC)进展的重要因素。胆汁酸(BA)代谢越来越被认为是肝-肠微生物群轴的关键参与者。

方法

本研究共纳入46例HBC患者和33名健康成年人。HBC患者分为BA正常组和BA高水平组。在患者日常饮食条件下采集粪便样本,对每个样本进行16S rRNA检测。

结果

与健康成年人相比,HBC患者肠道微生物群的α多样性显著改变,有益微生物群减少,机会性病原体增加。值得注意的是,BA高水平患者中芽孢杆菌、肠杆菌目、链球菌科、韦荣球菌属和乳杆菌目显著增加,而梭菌纲和梭菌目显著减少。HBC组中阿克曼菌科丰度降低,HBC患者中乳杆菌目显著富集,其丰度随BA升高而呈比例增加。

结论

这些发现为研究HBC中肠道微生物群与BA的相互作用提供了关键见解,有助于发现用于疾病监测的新型生物标志物,并开发以微生物群为靶点的治疗策略来调节BA代谢,以干预HBC的进展。

试验注册

本研究于2024年10月17日在中国临床试验注册中心(ChiCTR2400090990)注册(回顾性注册)。

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本文引用的文献

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Bile acid-mediated gut-liver axis crosstalk: the role of nuclear receptor signaling in dynamic regulation of inflammatory networks.胆汁酸介导的肠-肝轴串扰:核受体信号在炎症网络动态调节中的作用
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Gut Microbiota and the Gut-Liver Axis in Liver Disease: From Chronic Viral Hepatitis to Cirrhosis, Hepatocellular Carcinoma, and Microbiome-Based Therapies.肠道微生物群与肝脏疾病中的肠-肝轴:从慢性病毒性肝炎到肝硬化、肝细胞癌及基于微生物群的治疗方法
Microorganisms. 2025 Apr 30;13(5):1053. doi: 10.3390/microorganisms13051053.
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Dysregulation in the microbiota by HBV and HCV infection induces an altered cytokine profile in the pathobiome of infection.
乙肝病毒和丙肝病毒感染导致的微生物群失调会在感染病理生物群中诱导细胞因子谱改变。
Braz J Infect Dis. 2025 Jan-Feb;29(1):104468. doi: 10.1016/j.bjid.2024.104468. Epub 2024 Nov 28.
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Akkermansia muciniphila in the small intestine improves liver fibrosis in a murine liver cirrhosis model.小肠中的阿克曼氏菌可改善肝硬化小鼠模型的肝纤维化。
NPJ Biofilms Microbiomes. 2024 Sep 16;10(1):81. doi: 10.1038/s41522-024-00564-y.
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Bile acid-microbiota crosstalk in hepatitis B virus infection.乙型肝炎病毒感染中的胆汁酸-微生物群互作。
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Gut Microbiota and Biomarkers of Intestinal Barrier Damage in Cirrhosis.肝硬化患者的肠道微生物群与肠道屏障损伤的生物标志物
Microorganisms. 2024 Feb 25;12(3):463. doi: 10.3390/microorganisms12030463.
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Bile acids, gut microbiota, and therapeutic insights in hepatocellular carcinoma.胆汁酸、肠道微生物群与肝细胞癌的治疗新视角。
Cancer Biol Med. 2023 Dec 23;21(2):144-62. doi: 10.20892/j.issn.2095-3941.2023.0394.
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Gut Microbiota and Critically Ill Patients: Immunity and Its Modulation via Probiotics and Immunonutrition.肠道微生物群与危重症患者:通过益生菌和免疫营养调节免疫。
Nutrients. 2023 Aug 13;15(16):3569. doi: 10.3390/nu15163569.
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The regulatory role of bile acid microbiota in the progression of liver cirrhosis.胆汁酸微生物群在肝硬化进展中的调节作用。
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New Approaches to Chronic Hepatitis B.慢性乙型肝炎的新疗法
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