Metagenomics analysis of intestinal microbiota in patients with liver cirrhotic gastrointestinal bleeding before and after transjugular intrahepatic portosystemic shunt

doi:10.3877/cma.j.issn.2095-2015.2025.02.008

Abstract

Abstract:

Objective

To compare the characteristic changes in the structure and function of the intestinal microbiota in patients with liver cirrhotic gastrointestinal bleeding before and after transjugular intrahepatic portosystemic shunt （TIPS）.

Methods

A total of 20 patients with cirrhotic gastrointestinal bleeding admitted to the Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2020 to January 2024 were selected. Fecal samples before and after TIPS were collected，and fecal samples from 20 healthy volunteers were selected a as controls for metagenomic analysis.Subsequently，species and function annotations were conducted on the sequencing results，the differential flora，metabolic pathways and their correlation were analyzed.

Results

Compared with the healthy control group，patients with cirrhotic gastrointestinal bleeding showed a lower trend in the abundance and functional diversity of gut microbiota. There was no statistically significant difference in α-diversity between the pre-TIPS surgery group and the post-TIPS surgery group （P＞0.05）. However，a statistically significant difference in β-diversity was observed when comparing the three groups （P＜0.05）. The preliminary study revealed that after TIPS，the abundance of Enterobacteriaceae decreased，and the B/E ratio correspondingly increased. This reversed the downward trend of the B/E ratio caused by liver cirrhosis and thus enhanced the colonization resistance of gut bacteria. In terms of carbohydrate metabolism，the gut microbiota tended to shift from the genus Bacteroides，which was more effective in decomposing carbohydrates，to the genus Prevotella，which utilized plant-based carbohydrates. In terms of lipid metabolism，the abundance of butyrate-producing Ruminococcus in the intestine decreased.

Conclusion

There are significant differences in the structural and functional annotations of the intestinal microbiota in patients after TIPS，which may provide a potential novel microecological strategy for the prevention and treatment of postoperative complications of TIPS.

Key words: Liver cirrhosis, Transjugular intrahepatic portosystemic shunt, Gastrointestinal microbiome, Metagenomic

Yulin Wang, Zhonghua Wang, Ziwen Liu, Mengxin Lyu, Yuanzi Yu, Tao Li, Jinhua Hu, Xiaoqian Zhang. Metagenomics analysis of intestinal microbiota in patients with liver cirrhotic gastrointestinal bleeding before and after transjugular intrahepatic portosystemic shunt[J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2025, 15(02): 135-143.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhxhbyyxzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-2015.2025.02.008

https://zhxhbyyxzz.cma-cmc.com.cn/EN/Y2025/V15/I02/135

Figures/Tables 9

指标	入组患者（n=20）
年龄（岁， $\overset{ˉ}{x}$ ± s ）	53.90±9.67
性别［男，例（%）］	13（65.00）
乙型肝炎肝硬化［例（%）］	8（40.00）
终末期肝病模型评分（ $\overset{ˉ}{x}$ ± s ）	8.68±3.55
Child-Pugh 分级［例（%）］
A（5～6）	18（90.00）
B（7～9）	2（10.00）
C（10～13）	0
总蛋白（mg/dL， $\overset{ˉ}{x}$ ± s ）	56.55±8.85
白蛋白（mg/dL， $\overset{ˉ}{x}$ ± s ）	32.60±3.87
Cr（mg/Dl， P25，P75）	63.10（51.73～67.50）
ALT（U/L， P25，P75）	19.00（16.25～31.25）
AST（U/L， P25，P75）	24.50（21.25～34.00）
ALP（U/L， P25，P75）	80.00（59.75～109.75）
γ-GGT（U/L， P25，P75）	29.00（18.25～44.25）
PLT（10^-9/L， P25，P75）	82.50（46.25～137.00）
ALB（g/L， $\overset{ˉ}{x}$ ± s ）	32.60±3.87
TBIL（μmol/L， $\overset{ˉ}{x}$ ± s ）	21.97±9.98
PT（s， $\overset{ˉ}{x}$ ± s ）	13.15±1.64
INR （P25，P75）	1.19（1.08～1.33）

指标	入组患者（n=20）
年龄（岁， $\overset{ˉ}{x}$ ± s ）	53.90±9.67
性别［男，例（%）］	13（65.00）
乙型肝炎肝硬化［例（%）］	8（40.00）
终末期肝病模型评分（ $\overset{ˉ}{x}$ ± s ）	8.68±3.55
Child-Pugh 分级［例（%）］
A（5～6）	18（90.00）
B（7～9）	2（10.00）
C（10～13）	0
总蛋白（mg/dL， $\overset{ˉ}{x}$ ± s ）	56.55±8.85
白蛋白（mg/dL， $\overset{ˉ}{x}$ ± s ）	32.60±3.87
Cr（mg/Dl， P25，P75）	63.10（51.73～67.50）
ALT（U/L， P25，P75）	19.00（16.25～31.25）
AST（U/L， P25，P75）	24.50（21.25～34.00）
ALP（U/L， P25，P75）	80.00（59.75～109.75）
γ-GGT（U/L， P25，P75）	29.00（18.25～44.25）
PLT（10^-9/L， P25，P75）	82.50（46.25～137.00）
ALB（g/L， $\overset{ˉ}{x}$ ± s ）	32.60±3.87
TBIL（μmol/L， $\overset{ˉ}{x}$ ± s ）	21.97±9.98
PT（s， $\overset{ˉ}{x}$ ± s ）	13.15±1.64
INR （P25，P75）	1.19（1.08～1.33）

物种类别	A1 组内相对丰度均值	A2 组内相对丰度均值	B1 组内相对丰度均值
Phocaeicola	24.728	19.596	24.293
拟杆菌属	19.1994	13.635	9.5841
普雷沃菌属	4.4411	7.6499	17.5779
埃希菌属	2.945	4.1676	4.3806
Methanomassiliicoccus_A	3.128	3.0205	2.3978
链球菌属	2.1174	3.5343	4.6052
克雷伯菌属	1.8828	3.7177	1.9108
Blautia_A	3.3878	2.1033	1.4093
普拉梭菌属	1.5782	3.3793	4.0418
另枝菌属	2.9117	1.9345	1.0205
Enterocloster	3.0829	0.7003	1.562
韦荣球菌属	1.9687	1.6904	2.7856
副拟杆菌属	1.7682	1.2255	0.6856
罗氏菌属	1.1811	1.3468	1.463
瘤胃球菌属	1.9474	0.5388	0.1856
Gemmiger	0.884	1.5399	1.094
毛螺菌属	0.2182	2.0589	0.3741
Megasphaera	0.0604	2.0483	0.0575
Agathobacter	0.5245	1.3226	0.013
Ruthenibacterium	1.3439	0.321	0.6758
Mediterraneibacter	0.5226	0.734	0.3591
Sutterella	0.5999	0.5033	0.4157
Haemophilus_D	0.3739	0.6951	0.0687
CAG-83	0.3996	0.6499	0.6753
Collinsella	0.3306	0.7117	0.74
Prevotellamassilia	0.573	0.4659	0.0566
Ligilactobacillus	0.7456	0.2627	0.2408
Clostridium_Q	0.8303	0.1684	0.2827
Faecalimonas	0.875	0.0846	0.2453
Other	14.878	16.2017	16.3685

References 35

［1］	Simonetto DA，Liu M，Kamath PS. Portal Hypertension and Related Complications： Diagnosis and Management［J］. Mayo Clin Proc，2019，94（4）： 714-726.
［2］	Ginès P，Krag A，Abraldes JG，et al. Liver cirrhosis［J］. Lancet，2021，398（10308）： 1359-1376.
［3］	中华医学会消化病学分会消化微创介入协作组，唐承薇，张春清.经颈静脉肝内门体静脉分流术治疗门静脉高压专家共识［J］. 胃肠病学，2023，28（6）： 344-363.
［4］	Boike JR，Thornburg BG，Asrani SK，et al. North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension［J］. Clin Gastroenterol Hepatol，2022，20（8）： 1636-1662. e36.
［5］	de Franchis R，Bosch J，Garcia-Tsao G，et al. Baveno VII-Renewing consensus in portal hypertension［J］. J Hepatol，2022，76（4）： 959-974.
［6］	Tripathi A，Debelius J，Brenner DA，et al. The gut-liver axis and the intersection with the microbiome［J］. Nat Rev Gastroenterol Hepatol，2018，15（7）： 397-411.
［7］	Bajaj JS，Shamsaddini A，Fagan A，et al. Distinct gut microbial compositional and functional changes associated with impaired inhibitory control in patients with cirrhosis［J］. Gut Microbes，2021，13（1）： 1953247.
［8］	Huang L，Yu Q，Peng H，et al. Alterations of gut microbiome and effects of probiotic therapy in patients with liver cirrhosis： A systematic review and meta-analysis［J］. Medicine（Baltimore），2022，101（51）： e32335.
［9］	Jinato T，Sikaroodi M，Fagan A，et al. Alterations in gut virome are associated with cognitive function and minimal hepatic encephalopathy cross-sectionally and longitudinally in cirrhosis［J］. Gut Microbes，2023，15（2）： 2288168.
［10］	Swilling D，Patel A，Jesudian AB，et al. Impact of Transjugular Intrahepatic Shunt Creation on the Gut Microbiota［J］. J Vasc Interv Radiol，2024，35（3）： 469-472. e1.
［11］	Zhang H，Gao J. Antibiotics and probiotics on hepatic venous pressure gradient in cirrhosis： A systematic review and a meta-analysis［J］. PLoS One，2022，17（8）： e0273231.
［12］	Heller T，Herlemann D，Plieth A，et al. Liver cirrhosis and antibiotic therapy but not TIPS application leads to a shift of the intestinal bacterial communities： A controlled，prospective study［J］. J Dig Dis，2024，25（3）： 200-208.
［13］	Li D，Liu CM，Luo R，et al. MEGAHIT： an ultra-fast single-node solution for large and complex metagenomics assembly via succinct de Bruijn graph［J］. Bioinformatics，2015，31（10）： 1674-6.
［14］	Zhu W，Lomsadze A，Borodovsky M. Ab initio gene identification in metagenomic sequences［J］. Nucleic Acids Res，2010，38（12）： e132.
［15］	Fu L，Niu B，Zhu Z，et al. CD-HIT： accelerated for clustering the next-generation sequencing data［J］. Bioinformatics，2012，28（23）：3150-2.
［16］	Patro R，Duggal G，Love MI，et al. Salmon provides fast and bias-aware quantification of transcript expression［J］. Nat Methods，2017，14（4）： 417-419.
［17］	Buchfink B，Xie C，Huson DH. Fast and sensitive protein alignment using DIAMOND［J］. Nat Methods，2015，12（1）： 59-60.
［18］	Huerta-Cepas J，Szklarczyk D，Heller D，et al. eggNOG 5. 0： a hierarchical，functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses［J］. Nucleic Acids Res，2019，47（D1）： D309-D314.
［19］	Kanehisa M，Goto S. KEGG： kyoto encyclopedia of genes and genomes［J］. Nucleic Acids Res，2000，28（1）： 27-30.
［20］	Pal C，Bengtsson-Palme J，Rensing C，et al. BacMet： antibacterial biocide and metal resistance genes database［J］. Nucleic Acids Res，2014，42（Database issue）： D737-D743.
［21］	Jia B，Raphenya AR，Alcock B，et al. CARD 2017： expansion and model-centric curation of the comprehensive antibiotic resistance database［J］. Nucleic Acids Res，2017，45（D1）： D566-D573.
［22］	Galperin MY，Makarova KS，Wolf YI，et al. Expanded microbial genome coverage and improved protein family annotation in the COG database［J］. Nucleic Acids Res，2015，43（Database issue）：D261-D269.
［23］	Lombard V，Golaconda Ramulu H，Drula E，et al. The carbohydrate-active enzymes database（CAZy） in 2013［J］. Nucleic Acids Res，2014，42（Database issue）： D490-D495.
［24］	Poux S，Arighi CN，Magrane M，et al. On expert curation and scalability： UniProtKB/Swiss-Prot as a case study［J］. Bioinformatics，2017，33（21）： 3454-3460.
［25］	李萌浩，李凯，汤世豪，等. 轻微肝性脑病患者经颈静脉肝内门体分流术后不同预后组肠道菌群的变化［J］. 临床肝胆病杂志，2021，37（2）： 326-330.
［26］	苏红. 基于宏基因组学揭示大黄靶向肠道菌群改善创伤性脑损伤［D］. 长沙：中南大学，2023.
［27］	Bajaj JS，Hylemon PB，Ridlon JM，et al. Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation［J］. Am J Physiol Gastrointest Liver Physiol，2012，303（6）： G675-85.
［28］	吴仲文，李兰娟，马伟杭，等. 肠道微生物定植抗力的新指标—— B/E 值［J］. 浙江预防医学，2000（7）： 4-5.
［29］	Arumugam M，Raes J，Pelletier E，et al. Enterotypes of the human gut microbiome［J］. Nature，2011，473（7346）： 174-80.
［30］	Shu W，Shanjian C，Jinpiao L，et al. Gut microbiota dysbiosis in patients with hepatitis B virus-related cirrhosis［J］. Ann Hepatol，2022，27（2）： 100676.
［31］	Wei X，Yan X，Zou D，et al. Abnormal fecal microbiota community and functions in patients with hepatitis B liver cirrhosis as revealed by a metagenomic approach［J］. BMC Gastroenterol，2013，13： 175.
［32］	Raja G，Gupta H，Gebru YA，et al. Recent Advances of Microbiome-Associated Metabolomics Profiling in Liver Disease：Principles，Mechanisms，and Applications［J］. Int J Mol Sci，2021，22（3）： 1160.
［33］	Kespohl M，Vachharajani N，Luu M，et al. The Microbial Metabolite Butyrate Induces Expression of Th1-Associated Factors in CD4（+） T Cells［J］. Front Immunol，2017，8： 1036.
［34］	Martin-Gallausiaux C，Marinelli L，Blottière HM，et al. SCFA：mechanisms and functional importance in the gut［J］. Proc Nutr Soc，2021，80（1）： 37-49.
［35］	魏晓，邹大阳，闫夏贝，等. 肝硬化患者肠道微生物代谢功能的宏基因组学研究［J］. 军事医学，2013（11）： 801-807.

[1]	Lijun Wang, Honghong Zhang, Chunhuan Long. Metagenomics study of intestinal microbial community in patients with severe pneumonia and its predictive value for antibiotic treatment [J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2024, 18(06): 360-368.
[2]	Liuqing Wang, Ping Li, Xiaoshi Li, Yang Liu, Heling Wu, Guoping Zhou. Two cases of Chlamydia psittaci pneumonia first diagnosed in neurology department with headache and fatigue and literatures review [J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2024, 18(03): 176-181.
[3]	Meini Ye, Sijia Liu, Yuwei Zang, Yunjian Liu. Research progress on portal vein thrombosis in liver cirrhosis [J]. Chinese Archives of General Surgery(Electronic Edition), 2024, 18(05): 379-384.
[4]	Haoyuan Wang, Shu Wang, Juan Wang, Jianjun Yang. Research progress on the relationship between intestinal tract and gut microbiota based on organoid model [J]. Chinese Archives of General Surgery(Electronic Edition), 2024, 18(03): 220-224.
[5]	Xiaomei Qian, Hong Luo, Zhihui Li, Daijun Zhou, Dong Li. Logistic analysis of high-risk factors for primary liver cancer complicating hepatitis b-related liver cirrhosis in 76 cases [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2025, 19(03): 251-253.
[6]	Jian He, Li Zhang, Honghai Wang, Wentao Jiang. Research progress on the prognosis and treatment of hypersplenism after liver transplantation [J]. Chinese Journal of Transplantation(Electronic Edition), 2024, 18(05): 310-314.
[7]	Yidan Cai, Fang Jian, Zhiqiang Zhang, Li Chen, Shian Zhang, Lei Xia, Mei Ruan, Dongliang Li. Impact of transjugular intrahepatic portosystemic shunt on gut microbiota and liver function in patients with cirrhotic portal hypertension [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(05): 285-293.
[8]	Wanyu Deng, Fu Chen, Leibo Xu. Comparison of postoperative recurrence-free survival and analysis of influencing factors between hepatitis B-associated hepatocellular carcinoma patients with and without liver cirrhosis [J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2024, 13(05): 670-674.
[9]	Qifan Liu, An Jiang. Progress in non-invasive measurement of portal vein pressure in cirrhotic portal hypertension [J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2024, 13(03): 270-275.
[10]	Guangying Wu, Yanjuan Zhang, Peng Qin, Yanli Lu. Clinical study on prevention of upper gastrointestinal bleeding by transjugular intrahepatic portosystemic shunt [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2024, 14(06): 545-548.
[11]	Jian Cui, Qing Xia, Yun Lin, Guangling Li, Xinna Li, Wei Wang. Effects of platelet to lymphocyte ratio, immunoglobulin, myocardial enzyme spectrum and electrocardiogram parameters on the condition and prognosis of middle-aged and elderly patients with cirrhosis [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2024, 14(05): 400-406.
[12]	Xiangqing Qin, Chen Zhu, Haiyin Zhang. Construction of a normogram model for predicting the risk of esophageal and gastric varices bleeding in cirrhosis [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2024, 14(04): 330-335.
[13]	Yilong Liu, Rongguang Dang, Rong Ai, Kai Zhang. Establishment and validation of a model for the risk of rebleeding after endoscopic treatment in patients with cirrhosis and variceal bleeding [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2024, 14(04): 336-342.
[14]	Zexue Qi, Lianhui Zhao, Guangchuan Wang, Chunqing Zhang. Discuss of the progress of clinical application of transjugular intrahepatic portal shunt from domestic expert consensus recommendation [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2024, 14(03): 193-196.
[15]	Lin Qi, Ting Hong, Xin Wei, Hong Hu, Jiaqi Pu, Yunguo Liao, Xing Deng, Chao Li, Dan Deng, ZiYu Tang, Zhipeng Feng, Shixiang Qiu. Methodological study on constructing a liver phantom for training in transjugular intrahepatic portal shunt training [J]. Chinese Journal of Interventional Radiology(Electronic Edition), 2025, 13(01): 62-67.

Please choose a citation manager

Content to export