粪菌移植在慢性肝病治疗中的应用

徐洪凯; 汪春付; 张野; 连建奇

doi:10.3969/j.issn.1001-5256.2023.09.031

粪菌移植在慢性肝病治疗中的应用

DOI: 10.3969/j.issn.1001-5256.2023.09.031

空军军医大学第二附属医院传染科，西安 710038

基金项目:

陕西省重点研发计划 (2022SF－186)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：徐洪凯负责撰写论文；汪春付、张野负责修改论文；连建奇负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
连建奇， lianjq@fmmu.edu.cn （ORCID： 0000－0002－5549－7590）

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出版历程
- 收稿日期: 2022-11-21
- 录用日期: 2023-01-02
- 出版日期: 2023-09-19

Role of fecal microbiota transplantation in chronic liver diseases

Department of Infectious Diseases，The Second Affiliated Hospital of Air Force Medical University，Xi’an 710038，China

Research funding:

Shaanxi Province Key Research and Development Plan (2022SF－186)

More Information

Corresponding author: LIAN Jianqi， lianjq@fmmu.edu.cn （ORCID： 0000－0002－5549－7590）

摘要

摘要: 肠道菌群失调与慢性肝病的发生、发展及预后有着密切关系，而慢性肝病可加重肠道菌群失调，两者相互作用，相互影响。粪菌移植（FMT）通过移植健康捐献者的粪便菌群直接重建患者的肠道菌群并维持动态平衡，以达到目标治疗效果。近年来FMT作为重建肠道菌群的核心方法和肝脏疾病治疗方案的重要突破点得到了大量基础研究和临床试验的证实。本文就FMT在慢性肝病中的基础研究、临床研究及前景展望进行综述。
- 肝疾病 /
- 粪便微生物群移植 /
- 胃肠道微生物组
Abstract: Gut microbiota dysbiosis is closely associated with the development， progression， and prognosis of chronic liver diseases， while chronic liver diseases can aggravate gut microbiota dysbiosis， and the two interact with and influence each other. Through transplantation of fecal flora from healthy donors， fecal microbiota transplantation （FMT） directly reconstructs the intestinal flora of patients and maintains homeostasis， thereby achieving targeted therapeutic outcomes. In recent years， many basic research studies and clinical trials have proved FMT as a core therapeutic strategy for reconstructing intestinal flora and an important breakthrough point in treatment regimens for liver diseases. This article reviews the basic research， clinical studies， and future prospect of FMT in chronic liver diseases.
- Liver Diseases /
- Fecal Microbiota Transplantation /
- Gastrointestinal Microbiome

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表 1 各类慢性肝病经过FMT治疗后肠道菌群的变化

Table 1. Changes of intestinal flora after FMT treatment for various chronic liver diseases

疾病种类	第一作者，发表年份	类型	治疗/处理过程	菌群变化
非酒精代谢相关性疾病	叶毅，2019^［14］	临床试验	将非酒精代谢相关性疾病患者随机分为观察组和对照组，观察组行FMT和保肝药物治疗，对照组仅行保肝药物治疗	治疗3个月和6个月后观察组肠杆菌、葡萄球菌和肠球菌显著低于对照组，而双歧杆菌、拟杆菌、乳酸杆菌、普氏菌和普雷沃菌显著高于对照组
非酒精代谢相关性疾病	ZHOU D，2017^［54］	动物实验	将小鼠随机分为对照组、高脂饮食组和高脂饮食+FMT组。高脂食物喂养8周，FMT治疗8周。检测小鼠肠道微生物区系结构、盲肠内容物丁酸浓度、肝脏病理及肝内脂质和细胞因子	FMT组小鼠与高脂饮食组小鼠比较，菌群紊乱得到纠正，克里斯滕森菌科（属于厚壁菌门）和乳酸菌丰度增加，丁酸浓度上升
非酒精代谢相关性疾病	WITJES JJ， 2020^［55］	临床试验	将肝脂肪变性患者分为2组，每8周进行3次FMT，1组为异体供者，1组为自体供者，24周后对两组受试者的粪便菌群进行分析	异体供者组与瘤胃球菌、真细菌、粪杆菌和普氏菌有关的细菌的粪便微生物群丰度增加
酒精性肝病	PHILIPS CA， 2017^［19］	临床试验	对8例不符合皮质类固醇治疗条件的SAH男性患者进行FMT治疗，同期仅接受常规治疗的SAH患者为对照组，分别在6个月和1年后进行微生物群落分析	与常规治疗的SAH患者相比，FMT治疗的患者变形杆菌及肺炎克雷伯杆菌明显减少，放线杆菌、绒毛肠球菌、长双歧杆菌及埃氏巨噬菌数量上升
酒精性肝病	PHILIPS CA，2018^［20］	回顾性研究	对比了51例SAH患者的类固醇、营养疗法、己酮可可碱和FMT的治疗效果	FMT治疗8天后变形杆菌数量下降，厚壁菌门数量上升，FMT后30～90天梭状芽孢杆菌和拟杆菌增多，放线杆菌稳定，γ－变形杆菌减少，并新出现丹毒杆菌
肝硬化	BAJAJ JS，2019^［56］	临床试验	将15例患有肝性脑病的肝硬化患者随机分为2组，1组口服15粒FMT胶囊，1组服用安慰剂胶囊	FMT后30天与治疗前相比，十二指肠黏膜菌群多样性增加，十二指肠瘤胃球菌科和双歧杆菌科升高，面纱藻科降低。FMT组在第30天与安慰剂组相比，腊肠菌科和里肯内拉科数量升高
肝衰竭	高安，2021^［40］	动物实验	将40只小鼠分为正常组、模型组、粪菌移植组（选取正常组小鼠粪便作为粪菌供体）、模型小鼠粪菌移植组（选取模型组小鼠粪便作为粪菌供体），每组10只	与正常组小鼠相比，模型组小鼠疣微菌门，阿克曼菌属、Erysipelatoclostridium显著上升，Dubosiella、Duncaniella显著下降；模型小鼠粪菌移植组Faecalibaculum显著上升，Patescibacteria、脱铁杆菌门、Muribaculum、Candidatus－Saccharimonas、理研菌属、Odoribacter、Mucispirillum、Lachnospiraceae－unclassified显著下降。粪菌移植组小鼠Paramuribaculum、嗜胆菌属显著上升，厚壁菌门、Rikenella、Absiella显著下降
肝衰竭	LIU YM，2021^［41］	动物实验	选取20只小鼠，平均分为对照组、急性肝损伤模型组、FMT组、布拉酵母菌灌胃供体粪菌移植组，FMT组小鼠注射D－半乳糖胺后48 h口服粪便上清液100 mL，每24 h给予FMT 1次，共7次	经过FMT治疗后ALF小鼠的乳杆菌科、普氏菌科、S24－7、臭杆菌科和立克内菌科等菌群的比例恢复正常

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