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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2018, Vol. 12 Issue (2) : 123-129
Gut microbial balance and liver transplantation: alteration, management, and prediction
Xinyao Tian, Zhe Yang, Fangzhou Luo, Shusen Zheng()
Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
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Liver transplantation is a conventional treatment for terminal stage liver diseases. However, several complications still hinder the survival rate. Intestinal barrier destruction is widely observed among patients receiving liver transplant and suffering from ischemia–reperfusion or rejection injuries because of the relationship between the intestine and the liver, both in anatomy and function. Importantly, the resulting alteration of gut microbiota aggravates graft dysfunctions during the process. This article reviews the research progress for gut microbial alterations and liver transplantation. Especially, this work also evaluates research on the management of gut microbial alteration and the prediction of possible injuries utilizing microbial alteration during liver transplantation. In addition, we propose possible directions for research on gut microbial alteration during liver transplantation and offer a hypothesis on the utilization of microbial alteration in liver transplantation. The aim is not only to predict perioperative injuries but also to function as a method of treatment or even inhibit the rejection of liver transplantation.

Keywords gut microbial balance      liver transplantation      ischemia–reperfusion      acute rejection     
Corresponding Authors: Shusen Zheng   
Just Accepted Date: 30 October 2017   Online First Date: 28 December 2017    Issue Date: 02 April 2018
 Cite this article:   
Xinyao Tian,Zhe Yang,Fangzhou Luo, et al. Gut microbial balance and liver transplantation: alteration, management, and prediction[J]. Front. Med., 2018, 12(2): 123-129.
Fig.1  Liver IPC improved intestinal inflammation and barrier function following liver transplantation (LT) in rats. (A) Intestinal mucosal ultrastructure obtained by transmission electron microscopy (TEM) in rats following LT. MV, microvilli; TJ, tight junction. (B) Serum endotoxin was detected in the different groups. (C) sIgA content in feces was calculated by enzyme-linked immunosorbent assay (ELISA) and expressed as nanograms per gram wet feces in the different groups. (D) Serum tumor necrosis factor-α was determined by ELISA in the different groups. *P<0.05, **P<0.01, and ***P<0.001.
Fig.2  Dynamic alterations of hepatic graft function and structure during AR after OLT. (A) Representative hepatic graft histopathology stained with H&E (200×). (B) Representative hepatocyte ultrastructure observed by TEM. (C) Changes in plasma levels of ALT and AST at different time points after OLT. H&E, hematoxylin–eosin; TEM, transmission electron microscopy; AR, acute rejection; OLT, orthotopic liver transplantation; N, cell nucleus; M, mitochondria.
1 Sayegh MH, Carpenter CB. Transplantation 50 years later—progress, challenges, and promises. N Engl J Med 2004; 351(26): 2761–2766 pmid: 15616214
2 Hübscher SG. What is the long-term outcome of the liver allograft? J Hepatol 2011; 55(3): 702–717 pmid: 21426919
3 Bartosch S, Fite A, Macfarlane GT, McMurdo MET. Characterization of bacterial communities in feces from healthy elderly volunteers and hospitalized elderly patients by using real-time PCR and effects of antibiotic treatment on the fecal microbiota. Appl Environ Microbiol 2004; 70(6): 3575–3581 pmid: 15184159
4 Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. Diversity of the human intestinal microbial flora. Science 2005; 308(5728): 1635–1638 pmid: 15831718
5 Nenci A, Becker C, Wullaert A, Gareus R, van Loo G, Danese S, Huth M, Nikolaev A, Neufert C, Madison B, Gumucio D, Neurath MF, Pasparakis M. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 2007; 446(7135): 557–561 pmid: 17361131
6 Cani PD, Delzenne NM. The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Des 2009; 15(13): 1546–1558 pmid: 19442172
7 Hooper LV, Midtvedt T, Gordon JI. How host-microbial interactions shape the nutrient environment of the mammalian intestine. Annu Rev Nutr 2002; 22:283–307 pmid: 12055347
8 Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science 2005; 307(5717): 1915–1920 pmid: 15790844
9 Cicalese L, Sileri P, Green M, Abu-Elmagd K, Kocoshis S, Reyes J. Bacterial translocation in clinical intestinal transplantation. Transplantation 2001; 71(10): 1414–1417 pmid: 11391228
10 Nishida S, Levi D, Kato T, Nery JR, Mittal N, Hadjis N, Madariaga J, Tzakis AG. Ninety-five cases of intestinal transplantation at the University of Miami. J Gastrointest Surg 2002; 6(2): 233–239 pmid: 11992809
11 Guarner F, Malagelada JR. Gut flora in health and disease. Lancet 2003; 361(9356): 512–519 pmid: 12583961
12 Zoetendal EG, Collier CT, Koike S, Mackie RI, Gaskins HR. Molecular ecological analysis of the gastrointestinal microbiota: a review. J Nutr 2004; 134(2): 465–472
pmid: 14747690
13 Sheehy EC, Beighton D, Roberts GJ. The oral microbiota of children undergoing liver transplantation. Oral Microbiol Immunol 2000; 15(3): 203–210 pmid: 11154404
14 Kamada N, Calne RY. A surgical experience with five hundred thirty liver transplants in the rat. Surgery 1983; 93(1 Pt 1): 64–69
pmid: 6336859
15 Muyzer G, de Waal EC, Uitterlinden AG. Profiling of complex microbial populations by denaturing gradient gel electrophoresis analysis of polymerase chain reaction-amplified genes coding for 16S rRNA. Appl Environ Microbiol 1993; 59(3): 695–700
pmid: 7683183
16 Xing HC, Li LJ, Xu KJ, Shen T, Chen YB, Sheng JF, Chen Y, Fu SZ, Chen CL, Wang JG, Yan D, Dai FW, Zheng SS. Protective role of supplement with foreign Bifidobacterium and Lactobacillus in experimental hepatic ischemia-reperfusion injury. J Gastroenterol Hepatol 2006; 21(4): 647–656 pmid: 16677148
17 Westad F, Martens H. Variable selection in near infrared spectroscopy based on significance testing in partial least squares regression. J Near Infrared Spectrosc 2000; 8(2): 117–124
18 Barkholt L, Ericzon BG, Tollemar J, Malmborg AS, Ehrnst A, Wilczek H, Andersson J. Infections in human liver recipients: different patterns early and late after transplantation. Transpl Int 1993; 6(2): 77–84 pmid: 8447929
19 Thompson JR, Marcelino LA, Polz MF. Heteroduplexes in mixed-template amplifications: formation, consequence and elimination by ‘reconditioning PCR’. Nucleic Acids Res 2002; 30(9): 2083–2088 pmid: 11972349
20 Lipp JS, Morono Y, Inagaki F, Hinrichs KU. Significant contribution of Archaea to extant biomass in marine subsurface sediments. Nature 2008; 454(7207): 991–994 pmid: 18641632
21 Heilig HG, Zoetendal EG, Vaughan EE, Marteau P, Akkermans ADL, de Vos WM. Molecular diversity of Lactobacillus spp. and other lactic acid bacteria in the human intestine as determined by specific amplification of 16S ribosomal DNA. Appl Environ Microbiol 2002; 68(1): 114–123 pmid: 11772617
22 Wise MG, Siragusa GR. Quantitative analysis of the intestinal bacterial community in one- to three-week-old commercially reared broiler chickens fed conventional or antibiotic-free vegetable-based diets. J Appl Microbiol 2007; 102(4): 1138–1149
pmid: 17381758
23 Petra AI, Panagiotidou S, Hatziagelaki E, Stewart JM, Conti P, Theoharides TC. Gut-microbiota-brain axis and its effect on neuropsychiatric disorders with suspected immune dysregulation. Clin Ther 2015; 37(5): 984–995
24 Vanhoutte T, Huys G, Brandt E, Swings J. Temporal stability analysis of the microbiota in human feces by denaturing gradient gel electrophoresis using universal and group-specific 16S rRNA gene primers. FEMS Microbiol Ecol 2004; 48(3): 437–446 pmid: 19712312
25 Wu ZW, Ling ZX, Lu HF, Zuo J, Sheng JF, Zheng SS, Li LJ. Changes of gut bacteria and immune parameters in liver transplant recipients. Hepatobiliary Pancreat Dis Int 2012; 11(1): 40–50 pmid: 22251469
26 Wu ZW, Lu HF, Wu J, Zuo J, Chen P, Sheng JF, Zheng SS, Li LJ. Assessment of the fecal lactobacilli population in patients with hepatitis B virus-related decompensated cirrhosis and hepatitis B cirrhosis treated with liver transplant. Microb Ecol 2012; 63(4): 929–937 pmid: 21965156
27 Xing HC, Li LJ, Xu KJ, Shen T, Chen YB, Sheng JF, Yu YS, Chen YG. Intestinal microflora in rats with ischemia/reperfusion liver injury. J Zhejiang Univ Sci B 2005; 6(1): 14–21 pmid: 15593386
28 Xie Y, Luo Z, Li Z, Deng M, Liu H, Zhu B, Ruan B, Li L. Structural shifts of fecal microbial communities in rats with acute rejection after liver transplantation. Microb Ecol 2012; 64(2): 546–554 pmid: 22430504
29 Lu H, He J, Wu Z, Xu W, Zhang H, Ye P, Yang J, Zhen S, Li L. Assessment of microbiome variation during the perioperative period in liver transplant patients: a retrospective analysis. Microb Ecol 2013; 65(3): 781–791 pmid: 23504024
30 Groschwitz KR, Hogan SP. Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol 2009; 124(1): 3–20, quiz 21–22 pmid: 19560575
31 Jiang JW, Ren ZG, Chen LY, Jiang L, Xie HY, Zhou L, Zheng SS. Enteral supplementation with glycyl-glutamine improves intestinal barrier function after liver transplantation in rats. Hepatobiliary Pancreat Dis Int 2011; 10(4): 380–385 pmid: 21813386
32 Ren ZG, Liu H, Jiang JW, Jiang L, Chen H, Xie HY, Zhou L, Zheng SS. Protective effect of probiotics on intestinal barrier function in malnourished rats after liver transplantation. Hepatobiliary Pancreat Dis Int 2011; 10(5): 489–496 pmid: 21947722
33 Fasano A, Shea-Donohue T. Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol 2005; 2(9): 416–422 pmid: 16265432
34 Baumgart DC, Dignass AU. Intestinal barrier function. Curr Opin Clin Nutr Metab Care 2002; 5(6): 685–694 pmid: 12394645
35 Tapuria N, Kumar Y, Habib MM, Abu Amara M, Seifalian AM, Davidson BR. Remote ischemic preconditioning: a novel protective method from ischemia reperfusion injury—a review. J Surg Res 2008; 150(2): 304–330 pmid: 19040966
36 Ren Z, Cui G, Lu H, Chen X, Jiang J, Liu H, He Y, Ding S, Hu Z, Wang W, Zheng S. Liver ischemic preconditioning (IPC) improves intestinal microbiota following liver transplantation in rats through 16s rDNA-based analysis of microbial structure shift. PLoS One 2013; 8(10): e75950 pmid: 24098410
37 Xie Y, Chen H, Zhu B, Qin N, Chen Y, Li Z, Deng M, Jiang H, Xu X, Yang J, Ruan B, Li L. Effect of intestinal microbiota alteration on hepatic damage in rats with acute rejection after liver transplantation. Microb Ecol 2014; 68(4): 871–880 pmid: 25004996
38 Suau A, Bonnet R, Sutren M, Godon JJ, Gibson GR, Collins MD, Doré J. Direct analysis of genes encoding 16S rRNA from complex communities reveals many novel molecular species within the human gut. Appl Environ Microbiol 1999; 65(11): 4799–4807
pmid: 10543789
39 Shendure J, Ji H. Next-generation DNA sequencing. Nat Biotechnol 2008; 26(10): 1135–1145 pmid: 18846087
40 Wang WL, Xu SY, Ren ZG, Tao L, Jiang JW, Zheng SS. Application of metagenomics in the human gut microbiome. World J Gastroenterol 2015; 21(3): 803–814 pmid: 25624713
41 Oh PL, Martínez I, Sun Y, Walter J, Peterson DA, Mercer DF. Characterization of the ileal microbiota in rejecting and nonrejecting recipients of small bowel transplants. Am J Transplant 2012; 12(3): 753–762 pmid: 22152019
42 Lee JR, Muthukumar T, Dadhania D, Toussaint NC, Ling L, Pamer E, Suthanthiran M. Gut microbial community structure and complications after kidney transplantation: a pilot study. Transplantation 2014; 98(7): 697–705 pmid: 25289916
43 Jenq RR, Ubeda C, Taur Y, Menezes CC, Khanin R, Dudakov JA, Liu C, West ML, Singer NV, Equinda MJ, Gobourne A, Lipuma L, Young LF, Smith OM, Ghosh A, Hanash AM, Goldberg JD, Aoyama K, Blazar BR, Pamer EG, van den Brink MRM. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J Exp Med 2012; 209(5): 903–911 pmid: 22547653
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[2] Lei Li,Yimei Liu,Tiancheng Luo,Jian Zhou,Yingyong Hou,Xizhong Shen,Jiyao Wang. Comprehensive treatment of acute-on-chronic liver failure in a patient with hepatitis B: a case report[J]. Front. Med., 2014, 8(2): 250-253.
[3] Jiang LI, Yu HOU, Jing LIU, Bin LIU, Li LI. A better way to do small-for-size liver transplantation in rats[J]. Front Med, 2011, 5(1): 106-110.
[4] Nianqiao GONG, Xiaoping CHEN. Partial liver transplantation[J]. Front Med, 2011, 5(1): 1-7.
[5] Peng-Ji GAO, Xi-Sheng LENG, Dong WANG, Guang-Ming LI, Lei HUANG, Jie GAO, JI-Ye ZHU, . Graft versus host disease after liver transplantation: A case report[J]. Front. Med., 2010, 4(4): 469-472.
[6] YAN Lunan, WEN Tianfu, WANG Wentao, YANG Jiayin, XU Mingqing, CHEN Zheyu, WU Hong. Reducing biliary complications in adult-to-adult living donor liver transplantation using right lobe graft: experience of 124 cases[J]. Front. Med., 2008, 2(2): 130-133.
[7] LU Ling, ZHANG Feng, PU Liyong, YAO Aihua, YU Yue, SUN Beicheng, LI Guoqiang, WANG Xuehao. Biological features of intrahepatic CD4+CD25+ T cells in the naturally tolerance of rat liver transplantation[J]. Front. Med., 2007, 1(4): 373-376.
[8] ZHANG Feng, WANG Xuehao, LI Xiangcheng, KONG Lianbao, SUN Beicheng, LI Guoqiang, QIAN Xiaofen, CHEN Feng, WANG Ke, LU Sheng, PU Liyong, LU Ling. Emergency adult living donor right lobe liver transplantation for fulminant hepatic failure[J]. Front. Med., 2007, 1(3): 282-286.
[9] SHU Ming, PENG Chenghong, CHEN Hao, SHEN Boyong, ZHOU Guangwen, SHEN Chuan, LI Hongwei. Intra-abdominal hypertension is an independent cause of acute renal failure after orthotopic liver transplantation[J]. Front. Med., 2007, 1(2): 167-172.
[10] WANG Zhonggao. To restrict indication for stenting of the inferior vena cava and liver transplantation in patients with Budd-Chiari syndrome[J]. Front. Med., 2007, 1(2): 130-135.
[11] YAN Lunan, ZENG Yong, WEN Tianfu, ZHAO Jichun, WANG Wentao, YANG Jiayin, XU Mingqing, MA Yukui, CHEN Zheyu, LIU Jiangwen, WU Hong. Preliminary experience in adult-to-adult living donor liver transplantation in a single center in China[J]. Front. Med., 2007, 1(2): 136-141.
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