Intestinal Microbial Variation May Predict Early Acute Rejection after Liver Transplantation in Rats

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Abstract

Background

Acute rejection (AR) remains a life-threatening complication after orthotopic liver transplantation (OLT) and there are few available diagnostic biomarkers clinically for AR. This study aims to identify intestinal microbial profile and explore potential application of microbial profile as a biomarker for AR after OLT.

Methods

The OLT models in rats were established. Hepatic graft histology, ultrastructure, function, and intestinal barrier function were tested. Ileocecal contents were collected for intestinal microbial analysis.

Results

Hepatic graft suffered from the ischemia-reperfusion (I/R) injury on day 1, initial AR on day 3, and severe AR on day 7 after OLT. Real-time quantitative polymerase chain reaction results showed that genus Faecalibacterium prausnitzii and Lactobacillus were decreased, whereas Clostridium bolteae was increased during AR. Notably, cluster analysis of denaturing gradient gel electrophoresis (DGGE) profiles showed the 7AR and 3AR groups clustered together with 73.4% similarity, suggesting that intestinal microbiota was more sensitive than hepatic function in responding to AR. Microbial diversity and species richness were decreased during AR. Phylogenetic tree analysis showed that most of the decreased key bacteria belonged to phylum Firmicutes, whereas increased key bacteria belonged to phylum Bacteroidetes. Moreover, intestinal microvilli loss and tight junction damage were noted, and intestinal barrier dysfunction during AR presented a decrease of fecal secretory immunoglobulin A (sIgA) and increase of blood bacteremia, endotoxin, and tumor necrosis factor-α.

Conclusion

We dynamically detail intestinal microbial characterization and find a high sensitivity of microbial change during AR after OLT, suggesting that intestinal microbial variation may predict AR in early phase and become an assistant therapeutic target to improve rejection after OLT.

Abstract

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Most cited references 22

Record: found
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Article: not found

The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases.

Benoit Chassaing, Arlette Darfeuille-Michaud (2011)

Intestinal inflammation arises from abnormal host-microbe interactions. The perturbations of homeostatic coexistence involve host genetic factors, barrier function, innate and adaptive immunity, as well as qualitative and quantitative changes in the composition of the microbiota. Dysbiosis toward selected micro-organisms and decreased complexity of commensal bacteria have been observed in patients with Crohn's disease and ulcerative colitis, but it is not clear whether the dysbiosis contributes to development of inflammatory bowel disease or is instead a consequence of the disease. Pathogens with virulence factors that allow them to breach the intestinal barrier and induce chronic inflammation might mediate the pathogenesis of these diseases. To identify new therapeutic approaches for inflammatory bowel disease, it is important to identify host susceptibility factors involved in the control of microbial infection, characterize potential pathogens, and eliminate them or block the expression of their virulence factors. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

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Microbiota-liver axis in hepatic disease.

Benoit Chassaing, Lucie Etienne-Mesmin, Andrew Gewirtz (2014)

Accumulating evidence indicates that the gut microbiota, long appreciated to be a key determinant of intestinal inflammation, is also playing a key role in chronic inflammatory disease of the liver. Such studies have yielded a general central hypothesis whereby microbiota products activate the innate immune system to drive proinflammatory gene expression, thus promoting chronic inflammatory disease of the liver. This article reviews the background supporting this hypothesis, outlines how it can potentially explain classic and newly emerging epidemiological chronic inflammatory liver disease, and discusses potential therapeutic means to manipulate the microbiota so as to prevent and/or treat liver disease.

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Profound impact of gut homeostasis on chemically-induced pro-tumorigenic inflammation and hepatocarcinogenesis in rats.

Hui-Lu Zhang, Le-Xing Yu, Wen Yang … (2012)

Due to its anatomic connection, the liver is constantly exposed to gut-derived bacterial products or metabolites. Disruption of gut homeostasis is associated with many human diseases. The aim of this study was to determine the role of gut homeostasis in initiation and progression of hepatocellular carcinoma (HCC). Disruption of intestinal homeostasis by penicillin or dextran sulfate sodium (DSS) and its restoration by probiotics were applied in a diethylnitrosamine (DEN) model of rat hepatocarcinogenesis. Patients with liver cirrhosis and HCC had significantly increased serum endotoxin levels. Chronic DEN treatment of rats was associated with an imbalance of subpopulations of the gut microflora including a significant suppression of Lactobacillus species, Bifidobacterium species and Enterococcus species as well as intestinal inflammation. Induction of enteric dysbacteriosis or intestinal inflammation by penicillin or DSS, respectively, significantly promoted tumor formation. Administration of probiotics dramatically mitigated enteric dysbacteriosis, ameliorated intestinal inflammation, and most importantly, decreased liver tumor growth and multiplicity. Interestingly, probiotics not only inhibited the translocation of endotoxin, which bears pathogen-associated molecular patterns (PAMPs) but also the activation of damage-associated molecular patterns (DAMPs) such as high-mobility group box 1 (HMGB1). As a result, the production of pro- and anti-inflammatory cytokines was skewed in favor of a reduced tumorigenic inflammation in the liver. The data highlights the importance of gut homeostasis in the pathogenesis of HCC. Modulation of the gut microbiota by probiotics may represent a new avenue for therapeutic intervention to treat or prevent HCC development. Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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Author and article information

Journal

Journal ID (nlm-ta): Transplantation

Journal ID (iso-abbrev): Transplantation

Journal ID (publisher-id): TP

Title: Transplantation

Publisher: Lippincott Williams & Wilkins

ISSN (Print): 0041-1337

ISSN (Electronic): 1534-6080

Publication date (Print): 27 October 2014

Publication date (Electronic): 16 October 2014

Volume: 98

Issue: 8

Pages: 844-852

Affiliations

[1] ¹ Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

[2] ² Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

[3] ³ State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

[4] ⁴ Correspondence to: Lin Zhou, M.D., Ph.D., First Affiliated Hospital, School of Medicine, Zhejiang University, #79 Qingchun Road, Hangzhou, China.

[5] ⁵ Correspondence to: Shusen Zheng, M.D., Ph.D., First Affiliated Hospital, School of Medicine, Zhejiang University, #79 Qingchun Road, Hangzhou, China.

Author notes

E-mail: shusenzheng@ 123456zju.edu.cn . E-mail: zhoulin99@ 123456zju.edu.cn

Article

Publisher ID: TP140055 Accession ID: 00009

DOI: 10.1097/TP.0000000000000334

PMC ID: 4206351

PubMed ID: 25321166

SO-VID: 7c0aeec9-2445-4911-b222-cdc5ac57c3bf

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.

History

Date received : 18 February 2014

Date revision requested : 16 March 2014

Date accepted : 29 May 2014

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Keywords: liver transplantation,acute rejection,intestinal microbiota,microbiota-liver axis

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Keywords: liver transplantation, acute rejection, intestinal microbiota, microbiota-liver axis

Intestinal Microbial Variation May Predict Early Acute Rejection after Liver Transplantation in Rats

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Abstract

Background

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Microbial Genomics

Most cited references 22

The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases.

Microbiota-liver axis in hepatic disease.

Profound impact of gut homeostasis on chemically-induced pro-tumorigenic inflammation and hepatocarcinogenesis in rats.

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