Liver cirrhosis contributes to the disorder of gut microbiota in patients with hepatocellular carcinoma

Abstract Background Gut microbiota (GM) of patients with liver cancer is disordered, and syet no study reported the GM distribution of liver cirrhosis‐induced HCC (LC‐HCC) and nonliver cirrhosis‐induced HCC (NLC‐HCC). In this study, we aimed to characterize gut dysbiosis of LC‐HCC and NLC‐HCC to elu...

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Main Authors: Ruipeng Zheng, Guoqiang Wang, Zhiqiang Pang, Nan Ran, Yinuo Gu, Xuewa Guan, Yuze Yuan, Xu Zuo, He Pan, Jingtong Zheng, Fang Wang
Format: Article
Language:English
Published: Wiley 2020-06-01
Series:Cancer Medicine
Subjects:
Online Access:https://doi.org/10.1002/cam4.3045
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author Ruipeng Zheng
Guoqiang Wang
Zhiqiang Pang
Nan Ran
Yinuo Gu
Xuewa Guan
Yuze Yuan
Xu Zuo
He Pan
Jingtong Zheng
Fang Wang
author_facet Ruipeng Zheng
Guoqiang Wang
Zhiqiang Pang
Nan Ran
Yinuo Gu
Xuewa Guan
Yuze Yuan
Xu Zuo
He Pan
Jingtong Zheng
Fang Wang
author_sort Ruipeng Zheng
collection DOAJ
description Abstract Background Gut microbiota (GM) of patients with liver cancer is disordered, and syet no study reported the GM distribution of liver cirrhosis‐induced HCC (LC‐HCC) and nonliver cirrhosis‐induced HCC (NLC‐HCC). In this study, we aimed to characterize gut dysbiosis of LC‐HCC and NLC‐HCC to elucidate the role of GM in the pathogenesis of HCC. Methods A consecutive series of fecal samples of patients with hepatitis (24 patients), liver cirrhosis (24 patients), HCC (75 patients: 35 infected by HBV, 25 infected by HCV, and 15 with alcoholic liver disease), and healthy controls (20 patients) were obtained and sequenced on the Illumina Hiseq platform. The HCC group contains 52 LC‐HCC and 23 NLC‐HCC. Bioinformatic analysis of the intestinal microbiota was performed with QIIME and MicrobiomeAnalyst. Results Alpha‐diversity analysis showed that fecal microbial diversity was significantly decreased in the LC group, and there were significant differences in 3 phyla and 27 genera in the LC group vs the other groups (the healthy, hepatitis, and HCC groups). Beta‐diversity analysis showed that there were large differences between LC and the others. Gut microbial diversity was significantly increased from LC to HCC. Characterizing the fecal microbiota of LC‐HCC and NLC‐HCC, we found that microbial diversity was increased from LC to LC‐HCC rather than NLC‐HCC. Thirteen genera were discovered to be associated with the tumor size of HCC. Three biomarkers (Enterococcus, Limnobacter, and Phyllobacterium) could be used for precision diagnosis. We also found that HBV infection, HCV infection, or ALD (alcoholic liver disease) was not associated with intestinal microbial dysbiosis in HCC. Conclusion Our results suggest that GM disorders are more common in patients with LC‐HCC. The butyrate‐producing genera were decreased, while genera producing‐lipopolysaccharide (LPS) were increased in LC‐HCC patients. Further studies of GM disorders may achieve early diagnosis and new therapeutic approaches for HCC patients.
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spelling doaj.art-674a84579b3e417cae63227a75a9b0432022-12-22T04:01:04ZengWileyCancer Medicine2045-76342020-06-019124232425010.1002/cam4.3045Liver cirrhosis contributes to the disorder of gut microbiota in patients with hepatocellular carcinomaRuipeng Zheng0Guoqiang Wang1Zhiqiang Pang2Nan Ran3Yinuo Gu4Xuewa Guan5Yuze Yuan6Xu Zuo7He Pan8Jingtong Zheng9Fang Wang10Department of Pathogen Biology College of Basic Medical Sciences Jilin University Changchun ChinaDepartment of Pathogen Biology College of Basic Medical Sciences Jilin University Changchun ChinaDepartment of Pathogen Biology College of Basic Medical Sciences Jilin University Changchun ChinaDepartment of Pathogen Biology College of Basic Medical Sciences Jilin University Changchun ChinaDepartment of Pathogen Biology College of Basic Medical Sciences Jilin University Changchun ChinaDepartment of Pathogen Biology College of Basic Medical Sciences Jilin University Changchun ChinaDepartment of Pathogen Biology College of Basic Medical Sciences Jilin University Changchun ChinaDepartment of Pathogen Biology College of Basic Medical Sciences Jilin University Changchun ChinaDepartment of Pathogen Biology College of Basic Medical Sciences Jilin University Changchun ChinaDepartment of Pathogen Biology College of Basic Medical Sciences Jilin University Changchun ChinaDepartment of Pathogen Biology College of Basic Medical Sciences Jilin University Changchun ChinaAbstract Background Gut microbiota (GM) of patients with liver cancer is disordered, and syet no study reported the GM distribution of liver cirrhosis‐induced HCC (LC‐HCC) and nonliver cirrhosis‐induced HCC (NLC‐HCC). In this study, we aimed to characterize gut dysbiosis of LC‐HCC and NLC‐HCC to elucidate the role of GM in the pathogenesis of HCC. Methods A consecutive series of fecal samples of patients with hepatitis (24 patients), liver cirrhosis (24 patients), HCC (75 patients: 35 infected by HBV, 25 infected by HCV, and 15 with alcoholic liver disease), and healthy controls (20 patients) were obtained and sequenced on the Illumina Hiseq platform. The HCC group contains 52 LC‐HCC and 23 NLC‐HCC. Bioinformatic analysis of the intestinal microbiota was performed with QIIME and MicrobiomeAnalyst. Results Alpha‐diversity analysis showed that fecal microbial diversity was significantly decreased in the LC group, and there were significant differences in 3 phyla and 27 genera in the LC group vs the other groups (the healthy, hepatitis, and HCC groups). Beta‐diversity analysis showed that there were large differences between LC and the others. Gut microbial diversity was significantly increased from LC to HCC. Characterizing the fecal microbiota of LC‐HCC and NLC‐HCC, we found that microbial diversity was increased from LC to LC‐HCC rather than NLC‐HCC. Thirteen genera were discovered to be associated with the tumor size of HCC. Three biomarkers (Enterococcus, Limnobacter, and Phyllobacterium) could be used for precision diagnosis. We also found that HBV infection, HCV infection, or ALD (alcoholic liver disease) was not associated with intestinal microbial dysbiosis in HCC. Conclusion Our results suggest that GM disorders are more common in patients with LC‐HCC. The butyrate‐producing genera were decreased, while genera producing‐lipopolysaccharide (LPS) were increased in LC‐HCC patients. Further studies of GM disorders may achieve early diagnosis and new therapeutic approaches for HCC patients.https://doi.org/10.1002/cam4.3045gut microbiotahepatitishepatocellular carcinomaliver cirrhosis
spellingShingle Ruipeng Zheng
Guoqiang Wang
Zhiqiang Pang
Nan Ran
Yinuo Gu
Xuewa Guan
Yuze Yuan
Xu Zuo
He Pan
Jingtong Zheng
Fang Wang
Liver cirrhosis contributes to the disorder of gut microbiota in patients with hepatocellular carcinoma
Cancer Medicine
gut microbiota
hepatitis
hepatocellular carcinoma
liver cirrhosis
title Liver cirrhosis contributes to the disorder of gut microbiota in patients with hepatocellular carcinoma
title_full Liver cirrhosis contributes to the disorder of gut microbiota in patients with hepatocellular carcinoma
title_fullStr Liver cirrhosis contributes to the disorder of gut microbiota in patients with hepatocellular carcinoma
title_full_unstemmed Liver cirrhosis contributes to the disorder of gut microbiota in patients with hepatocellular carcinoma
title_short Liver cirrhosis contributes to the disorder of gut microbiota in patients with hepatocellular carcinoma
title_sort liver cirrhosis contributes to the disorder of gut microbiota in patients with hepatocellular carcinoma
topic gut microbiota
hepatitis
hepatocellular carcinoma
liver cirrhosis
url https://doi.org/10.1002/cam4.3045
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