肠道菌群介导胆汁酸影响炎症性肠病的研究进展

doi:10.3969/j.issn.1674-8115.2024.07.005

上海交通大学学报（医学版） ›› 2024, Vol. 44 ›› Issue (7): 839-846.doi: 10.3969/j.issn.1674-8115.2024.07.005

• 转化医学研究前沿进展专题 • 上一篇

肠道菌群介导胆汁酸影响炎症性肠病的研究进展

夏西茜¹(), 丁珂珂¹, 张慧恒¹, 彭旭飞¹, 孙昳旻¹, 唐雅珺¹, 汤晓芳²()

^1.上海交通大学医学院附属第六人民医院转化医学中心，上海 200233
^2.上海交通大学医学院附属上海市第一人民医院临床研究院，上海 200080

收稿日期:2024-01-30 接受日期:2024-04-03 出版日期:2024-07-28 发布日期:2024-07-28
通讯作者: 汤晓芳 E-mail:xiaxixi0715@163.com;tangxiaofang19840@163.com
作者简介:夏西茜（2000—），女，硕士生；电子信箱：xiaxixi0715@163.com。
基金资助:
上海市白玉兰人才计划浦江项目(23PJ1410700)

Research progress of the role of intestinal microbiota-mediated bile acids in inflammatory bowel disease

XIA Xixi¹(), DING Keke¹, ZHANG Huiheng¹, PENG Xufei¹, SUN Yimin¹, TANG Yajun¹, TANG Xiaofang²()

^1.Center for Translational Medicine, Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
^2.Clinical Research Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China

Received:2024-01-30 Accepted:2024-04-03 Online:2024-07-28 Published:2024-07-28
Contact: TANG Xiaofang E-mail:xiaxixi0715@163.com;tangxiaofang19840@163.com
Supported by:
Shanghai Magnolia Talent Plan Pujiang Project(23PJ1410700)

摘要/Abstract

摘要：

据估计，全球约有700万人受炎症性肠病（inflammatory bowel disease，IBD）的影响，对医疗系统和社会造成了极大负担。在IBD的发生、进展及治疗过程中，肠道菌群及其关键代谢产物——胆汁酸扮演着至关重要的角色。肠道菌群不仅参与胆汁酸的生物转化，丰富胆汁酸的多样性，还通过法尼酯X受体（farnesoid X receptor，FXR）调控其合成与转运过程。同时，胆汁酸亦通过对微生物多样性的支持、直接毒性、间接抗微生物途径和对微生物代谢能力的影响，参与调整肠道菌群的结构和功能。此外，在正常生理条件下，经肠道菌群修饰后的胆汁酸能够促进肠上皮屏障的损伤修复过程，并且通过调节辅助性T细胞（helper T cell，Th细胞）17、调节性T细胞（regulatory T cell，Treg细胞）、CD8⁺T细胞和自然杀伤T细胞（natural killer T cell，NKT细胞）等多种免疫细胞功能，促进免疫系统的平衡，减缓IBD的发展。该文重点探讨了肠道菌群通过介导胆汁酸在IBD的发生和发展中发挥的作用，并探索以肠道菌群和胆汁酸为靶点的新型有效治疗策略，如胆汁酸受体调节剂、益生菌和益生元干预、粪便菌群移植（fecal microbiota transplantation，FMT）以及噬菌体疗法等。

关键词: 肠道菌群, 胆汁酸, 炎症性肠病, 代谢物

Abstract:

It is estimated that approximately seven million people worldwide are affected by inflammatory bowel disease (IBD), causing a huge burden on healthcare systems and society. In the occurrence, progression, and treatment of IBD, the intestinal microbiota and its key metabolic product, bile acids, play a crucial role. The intestinal microbiota not only participates in the biotransformation of bile acids, enriching the diversity of bile acids, but also regulates their synthesis and transport through the farnesoid X receptor (FXR). Meanwhile, bile acids contribute to regulating the structure and function of the intestinal microbiota by supporting microbial diversity, exerting direct toxicity, participating in indirect antimicrobial pathways, and influencing microbial metabolic capabilities. Furthermore, under normal physiological conditions, intestinal microbiota-derived bile acids facilitate the repair process of the intestinal epithelial barrier. They also promote the balance of the immune system by modulating the functions of various immune cells including helper T (Th) cells 17, regulatory T (Treg) cells, CD8⁺ T cells and natural killer T(NKT) cells, thereby slowing down the development of IBD. This article focuses on exploring the role of intestinal microbiota and bile acids in the onset and progression of IBD, and investigating new effective treatment strategies by targeting intestinal microbiota and bile acids, such as bile acid receptor modulators, probiotics, prebiotics, fecal microbiota transplantation (FMT), and phage therapy.

Key words: intestinal microbiota, bile acid, inflammatory bowel disease (IBD), metabolite

中图分类号:

R574

夏西茜, 丁珂珂, 张慧恒, 彭旭飞, 孙昳旻, 唐雅珺, 汤晓芳. 肠道菌群介导胆汁酸影响炎症性肠病的研究进展[J]. 上海交通大学学报（医学版）, 2024, 44(7): 839-846.

XIA Xixi, DING Keke, ZHANG Huiheng, PENG Xufei, SUN Yimin, TANG Yajun, TANG Xiaofang. Research progress of the role of intestinal microbiota-mediated bile acids in inflammatory bowel disease[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(7): 839-846.

图/表 2

表1 IBD患者肠道菌群的特征性变化

Tab 1 Intestinal microbial signatures in patients with IBD

Phylum	Genus (species)	Imbalance in IBD patient
Proteobacteria	Escherichia (AIEC)	↑
Bacteroidetes	Bacteroides (ETBF)	↑
Fusobacteria	Fusobacterium	↑
Firmicutes	Ruminococcus	↑
	Roseburia	↓
	Faecalibacterium (Faecalibacterium prausnitzii)	↓
Actinobacteria	Bifidobacterium	↓
Verrucomicrobia	Akkermansia (Akkermansia muciniphila)	↓

图1 肠道菌群通过调节FXR影响胆汁酸代谢Note： BAAT—bile acid-CoA: amino acid N-acyltransferase; BACS—bile acid coenzyme A synthetase; T/G CDCA—taurochenodeoxycholic/glycochenodeoxycholic acid; T/G CA—taurocholate/ glycocholic acid.

Fig1 Intestinal microbiota affects bile acids metabolism by regulating FXR

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肠道菌群介导胆汁酸影响炎症性肠病的研究进展

Research progress of the role of intestinal microbiota-mediated bile acids in inflammatory bowel disease

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