肝移植术后肠道菌群失调的诊疗策略

鲍志野; 刘浩

doi:10.3969/j.issn.1674-7445.2022.04.009

肝移植术后肠道菌群失调的诊疗策略

doi: 10.3969/j.issn.1674-7445.2022.04.009

鲍志野,
刘浩^,

110001 沈阳，中国医科大学附属第一医院器官移植暨肝胆外科辽宁省器官移植重点实验室（鲍志野）；中国医科大学附属盛京医院肝胆移植外科（刘浩）

基金项目:

国家自然科学基金项目 81373173

详细信息

作者简介:

通讯作者:
刘浩，Email：liuhaodoctor@hotmail.com

中图分类号: R617, Q939.121
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- 被引次数: 0
出版历程
- 收稿日期: 2022-03-03
- 网络出版日期: 2022-07-14
- 刊出日期: 2022-07-15

Diagnosis and treatment strategy of intestinal flora imbalance after liver transplantation

Bao Zhiye,
Liu Hao^,

Department of Organ Transplantation and Hepatobiliary Surgery, the First Hospital of China Medical University, Key Laboratory of Organ Transplantation of Liaoning Province, Shenyang 110001, China

More Information

Corresponding author: Liu Hao, Email: liuhaodoctor@hotmail.com

摘要

摘要: 肝移植术后会发生多种近期以及远期并发症。在术后早期，由于多重耐药菌的产生很容易导致各种感染，其中之一表现为肠道菌群失调。在过去的十年中，一系列研究发现肠道菌群在维持肠道稳态方面具有重要功能。肠道菌群通过多种途径与其他器官相互影响，其中肠肝轴是最关键的体内微环境调节通道之一。肠道菌群在数量和成分上的改变均能导致肠道菌群失调。无论在局部还是全身系统，肠道菌群与免疫系统都存在广泛的交互作用。本文着重探讨肝移植术后肠道菌群失调发生的危险因素、肠道菌群失调对肝移植受者的影响以及相关的治疗方案。
- 肝移植 /
- 肠道菌群失调 /
- 益生菌 /
- 粪便菌群移植 /
- 短链脂肪酸 /
- Shannon多样性指数 /
- 全肠外营养(TPN) /
- 选择性消化道去污(SDD)
Abstract: Multiple short-term and long-term complications might occur after liver transplantation. In the early stage after liver transplantation, the incidence of multidrug-resistant bacteria is likely to cause different types of infection, one of which is intestinal flora imbalance. In the recent decade, a series of studies have demonstrated that intestinal flora plays an important role in maintaining intestinal homeostasis. Intestinal flora may interact with other organs via multiple patterns. Among which, gut-liver axis is one of the most critical channels for regulating microenvironment of the host. Changes in the quantity and composition of intestinal flora could lead to intestinal flora imbalance. In both local and systemic systems, extensive interaction exists between intestinal flora and immune system. In this article, the risk factors of intestinal flora imbalance after liver transplantation, influence of intestinal flora imbalance on liver transplant recipients and relevant treatment strategies were reviewed.
- Liver transplantation /
- Intestinal flora imbalance /
- Probiotics /
- Fecal microbiota transplantation /
- Short chain fatty acid /
- Shannon diversity index /
- Total parenteral nutrition (TPN) /
- Selective decontamination of the digestive tract (SDD)

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参考文献(45)

[1]	KRISS M, VERNA EC, ROSEN HR, et al. Functional microbiomics in liver transplantation: identifying novel targets for improving allograft outcomes[J]. Transplantation, 2019, 103(4): 668-678. DOI: 10.1097/TP.0000000000002568.
[2]	ANCONA G, ALAGNA L, LOMBARDI A, et al. The interplay between gut microbiota and the immune system in liver transplant recipients and its role in infections[J]. Infect Immun, 2021, 89(11): e0037621. DOI: 10.1128/IAI.00376-21.
[3]	OH HS, MIN U, JANG H, et al. Proposal of a health gut microbiome index based on a Meta-analysis of Korean and global population datasets[J]. J Microbiol, 2022, 60(5): 533-549. DOI: 10.1007/s12275-022-1526-0.
[4]	AHLAWAT S, ASHA, SHARMA KK. Gut-organ axis: a microbial outreach and networking[J]. Lett Appl Microbiol, 2021, 72(6): 636-668. DOI: 10.1111/lam.13333.
[5]	YAN S, YIN XM. Gut microbiome in liver pathophysiology and cholestatic liver disease[J]. Liver Res, 2021, 5(3): 151-163. DOI: 10.1016/j.livres.2021.08.001.
[6]	BAJAJ JS, KHORUTS A. Microbiota changes and intestinal microbiota transplantation in liver diseases and cirrhosis[J]. J Hepatol, 2020, 72(5): 1003-1027. DOI: 10.1016/j.jhep.2020.01.017.
[7]	PIROZZOLO I, LI Z, SEPULVEDA M, et al. Influence of the microbiome on solid organ transplant survival[J]. J Heart Lung Transplant, 2021, 40(8): 745-753. DOI: 10.1016/j.healun.2021.04.004.
[8]	ZHENG D, LIWINSKI T, ELINAV E. Interaction between microbiota and immunity in health and disease[J]. Cell Res, 2020, 30(6): 492-506. DOI: 10.1038/s41422-020-0332-7.
[9]	MONGODIN EF, SAXENA V, IYYATHURAI J, et al. Chronic rejection as a persisting phantom menace in organ transplantation: a new hope in the microbiota?[J]. Curr Opin Organ Transplant, 2021, 26(6): 567-581. DOI: 10.1097/MOT.0000000000000929.
[10]	DERY KJ, KADONO K, HIRAO H, et al. Microbiota in organ transplantation: an immunological and therapeutic conundrum?[J]. Cell Immunol, 2020, 351: 104080. DOI: 10.1016/j.cellimm.2020.104080.
[11]	FU PP, XIONG F, WU SG, et al. Effects of schyzocotyle acheilognathi (Yamaguti, 1934) infection on the intestinal microbiota, growth and immune reactions of grass carp (ctenopharyngodon idella)[J]. PLoS One, 2022, 17(4): e0266766. DOI: 10.1371/journal.pone.0266766.
[12]	YANG XA, LV F, WANG R, et al. Potential role of intestinal microflora in disease progression among patients with different stages of hepatitis B[J]. Gut Pathog, 2020, 12: 50. DOI: 10.1186/s13099-020-00391-4.
[13]	SOLÉ C, GUILLY S, DA SILVA K, et al. Alterations in gut microbiome in cirrhosis as assessed by quantitative metagenomics: relationship with acute-on-chronic liver failure and prognosis[J]. Gastroenterology, 2021, 160(1): 206-218. DOI: 10.1053/j.gastro.2020.08.054.
[14]	BAJAJ JS, KAKIYAMA G, COX IJ, et al. Alterations in gut microbial function following liver transplant[J]. Liver Transpl, 2018, 24(6): 752-761. DOI: 10.1002/lt.25046.
[15]	CHEN Y, GUO J, QIAN G, et al. Gut dysbiosis in acute-on-chronic liver failure and its predictive value for mortality[J]. J Gastroenterol Hepatol, 2015, 30(9): 1429-1437. DOI: 10.1111/jgh.12932.
[16]	BAJAJ JS, HEUMAN DM, HYLEMON PB, et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications[J]. J Hepatol, 2014, 60(5): 940-947. DOI: 10.1016/j.jhep.2013.12.019.
[17]	GRĄT M, HOŁÓWKO W, WRONKA KM, et al. The relevance of intestinal dysbiosis in liver transplant candidates[J]. Transpl Infect Dis, 2015, 17(2): 174-184. DOI: 10.1111/tid.12352.
[18]	CORNIDE-PETRONIO ME, ÁLVAREZ-MERCADO AI, JIMÉNEZ-CASTRO MB, et al. Current knowledge about the effect of nutritional status, supplemented nutrition diet, and gut microbiota on hepatic ischemia-reperfusion and regeneration in liver surgery[J]. Nutrients, 2020, 12(2): 284. DOI: 10.3390/nu12020284.
[19]	OIKONOMOU T, PAPATHEODORIDIS GV, SAMARKOS M, et al. Clinical impact of microbiome in patients with decompensated cirrhosis[J]. World J Gastroenterol, 2018, 24(34): 3813-3820. DOI: 10.3748/wjg.v24.i34.3813.
[20]	BAJAJ JS, IDILMAN R, MABUDIAN L, et al. Diet affects gut microbiota and modulates hospitalization risk differentially in an international cirrhosis cohort[J]. Hepatology, 2018, 68(1): 234-247. DOI: 10.1002/hep.29791.
[21]	FILOS KS, KIRKILESIS I, SPILIOPOULOU I, et al. Bacterial translocation, endotoxaemia and apoptosis following Pringle manoeuvre in rats[J]. Injury, 2004, 35(1): 35-43. DOI: 10.1016/s0020-1383(03)00288-2.
[22]	LA ROSA R, JOHANSEN HK, MOLIN S. Persistent bacterial infections, antibiotic treatment failure, and microbial adaptive evolution[J]. Antibiotics (Basel), 2022, 11(3): 419. DOI: 10.3390/antibiotics11030419.
[23]	ZAZA G, DALLA GASSA A, FELIS G, et al. Impact of maintenance immunosuppressive therapy on the fecal microbiome of renal transplant recipients: comparison between an everolimus- and a standard tacrolimus-based regimen[J]. PLoS One, 2017, 12(5): e0178228. DOI: 10.1371/journal.pone.0178228.
[24]	JARDOU M, PROVOST Q, BROSSIER C, et al. Alteration of the gut microbiome in mycophenolate-induced enteropathy: impacts on the profile of short-chain fatty acids in a mouse model[J]. BMC Pharmacol Toxicol, 2021, 22(1): 66. DOI: 10.1186/s40360-021-00536-4.
[25]	TIAN X, YANG Z, LUO F, et al. Gut microbial balance and liver transplantation: alteration, management, and prediction[J]. Front Med, 2018, 12(2): 123-129. DOI: 10.1007/s11684-017-0563-2.
[26]	XIE Y, LUO Z, LI Z, et al. Structural shifts of fecal microbial communities in rats with acute rejection after liver transplantation[J]. Microb Ecol, 2012, 64(2): 546-554. DOI: 10.1007/s00248-012-0030-1.
[27]	JIANG JW, REN ZG, CUI GY, et al. Chronic bile duct hyperplasia is a chronic graft dysfunction following liver transplantation[J]. World J Gastroenterol, 2012, 18(10): 1038-1047. DOI: 10.3748/wjg.v18.i10.1038.
[28]	ANNAVAJHALA MK, GOMEZ-SIMMONDS A, MACESIC N, et al. Colonizing multidrug-resistant bacteria and the longitudinal evolution of the intestinal microbiome after liver transplantation[J]. Nat Commun, 2019, 10(1): 4715. DOI: 10.1038/s41467-019-12633-4.
[29]	GUO Y, CRNKOVIC CM, WON KJ, et al. Commensal gut bacteria convert the immunosuppressant tacrolimus to less potent metabolites[J]. Drug Metab Dispos, 2019, 47(3): 194-202. DOI: 10.1124/dmd.118.084772.
[30]	ZHANG Z, LIU L, TANG H, et al. Immunosuppressive effect of the gut microbiome altered by high-dose tacrolimus in mice[J]. Am J Transplant, 2018, 18(7): 1646-1656. DOI: 10.1111/ajt.14661.
[31]	JIA J, TIAN X, JIANG J, et al. Structural shifts in the intestinal microbiota of rats treated with cyclosporine A after orthotropic liver transplantation[J]. Front Med, 2019, 13(4): 451-460. DOI: 10.1007/s11684-018-0675-3.
[32]	LI R, XIE L, LI L, et al. The gut microbial metabolite, 3, 4-dihydroxyphenylpropionic acid, alleviates hepatic ischemia/reperfusion injury via mitigation of macrophage pro-inflammatory activity in mice[J]. Acta Pharm Sin B, 2022, 12(1): 182-196. DOI: 10.1016/j.apsb.2021.05.029.
[33]	KATCHMAN E, MARQUEZ M, BAZERBACHI F, et al. A comparative study of the use of selective digestive decontamination prophylaxis in living-donor liver transplant recipients[J]. Transpl Infect Dis, 2014, 16(4): 539-547. DOI: 10.1111/tid.12235.
[34]	SORBARA MT, DUBIN K, LITTMANN ER, et al. Inhibiting antibiotic-resistant Enterobacteriaceae by microbiota-mediated intracellular acidification[J]. J Exp Med, 2019, 216(1): 84-98. DOI: 10.1084/jem.20181639.
[35]	ZHANG J, REN FG, LIU P, et al. Characteristics of fecal microbial communities in patients with non-anastomotic biliary strictures after liver transplantation[J]. World J Gastroenterol, 2017, 23(46): 8217-8226. DOI: 10.3748/wjg.v23.i46.8217.
[36]	KAHN J, PREGARTNER G, SCHEMMER P. Effects of both pro- and synbiotics in liver surgery and transplantation with special focus on the gut-liver axis-a systematic review and Meta-analysis[J]. Nutrients, 2020, 12(8): 2461. DOI: 10.3390/nu12082461.
[37]	KIM SG, BECATTINI S, MOODY TU, et al. Microbiota-derived lantibiotic restores resistance against vancomycin-resistant enterococcus[J]. Nature, 2019, 572(7771): 665-669. DOI: 10.1038/s41586-019-1501-z.
[38]	CHONG PP, KOH AY. The gut microbiota in transplant patients[J]. Blood Rev, 2020, 39: 100614. DOI: 10.1016/j.blre.2019.100614.
[39]	BAJAJ JS, SHAMSADDINI A, FAGAN A, et al. Fecal microbiota transplant in cirrhosis reduces gut microbial antibiotic resistance genes: analysis of two trials[J]. Hepatol Commun, 2020, 5(2): 258-271. DOI: 10.1002/hep4.1639.
[40]	MCDONALD LC, GERDING DN, JOHNSON S, et al. Clinical practice guidelines for clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)[J]. Clin Infect Dis, 2018, 66(7): e1-e48. DOI: 10.1093/cid/cix1085.
[41]	SCHLUGER A, ROSENBLATT R, KNOTTS R, et al. Clostridioides difficile infection and recurrence among 2622 solid organ transplant recipients[J]. Transpl Infect Dis, 2019, 21(6): e13184. DOI: 10.1111/tid.13184.
[42]	CHENG YW, PHELPS E, GANAPINI V, et al. Fecal microbiota transplantation for the treatment of recurrent and severe clostridium difficile infection in solid organ transplant recipients: a multicenter experience[J]. Am J Transplant, 2019, 19(2): 501-511. DOI: 10.1111/ajt.15058.
[43]	QURAISHI MN, WIDLAK M, BHALA N, et al. Systematic review with Meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory clostridium difficile infection[J]. Aliment Pharmacol Ther, 2017, 46(5): 479-493. DOI: 10.1111/apt.14201.
[44]	HALAWEISH HF, BOATMAN S, STALEY C. Encapsulated fecal microbiota transplantation: development, efficacy, and clinical application[J]. Front Cell Infect Microbiol, 2022, 12: 826114. DOI: 10.3389/fcimb.2022.826114.
[45]	DEFILIPP Z, BLOOM PP, TORRES SOTO M, et al. Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant[J]. N Engl J Med, 2019, 381(21): 2043-2050. DOI: 10.1056/NEJMoa1910437.