Multi-Omics Analyses Identify Signatures in Patients with Liver Cirrhosis and Hepatocellular Carcinoma
Gut bacterial/viral dysbiosis, changes in circulating metabolites, and plasma cytokines/chemokines have been previously associated with various liver diseases. Here, we analyzed the associations between fecal microbial composition, circulating metabolites, and plasma cytokines/chemokines in patients...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/1/210 |
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| author | Ming-Wei Lai Yu-De Chu Chao-Wei Hsu Yi-Cheng Chen Kung-Hao Liang Chau-Ting Yeh |
| author_facet | Ming-Wei Lai Yu-De Chu Chao-Wei Hsu Yi-Cheng Chen Kung-Hao Liang Chau-Ting Yeh |
| author_sort | Ming-Wei Lai |
| collection | DOAJ |
| description | Gut bacterial/viral dysbiosis, changes in circulating metabolites, and plasma cytokines/chemokines have been previously associated with various liver diseases. Here, we analyzed the associations between fecal microbial composition, circulating metabolites, and plasma cytokines/chemokines in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC). We recruited 10 HCC patients, 18 LC patients, and 17 healthy individuals. Their stool samples were used for gene sequencing of bacterial 16S rRNA and viral genomes, while plasma samples were utilized for the determination of endotoxin, zonulin, metabolite, and cytokine/chemokine levels. Dysbiosis was observed among gut bacteria and viruses, with significant changes in abundance at the genus and species levels, respectively. However, no differences were found between cohorts in the alpha and beta diversity. Plasma lipopolysaccharides and zonulin, but not trimethylamine N-oxide, were progressively increased in LC and HCC subjects. Profiling plasma metabolites and selected cytokines/chemokines revealed differential changes in the LC and HCC cohorts. Following joint correlation and correlation network analyses, regardless of etiology, common network signatures shared by LC and HCC patients were characterized by the gut virus Stenotrophomonas virus DLP5 and the uncultured Caudovirales phage, plasma metabolites pyruvic acid and acetic acid, and plasma cytokines/chemokines eotaxin and PDGF-AB/BB, respectively. Additionally, LC- and HCC-specific correlation networks were also identified. This study provides novel insights into altered gut microbial/viral composition that may contribute to pre-HCC disorders, metabolic reprogramming, or inflammatory microenvironments for hepatocarcinogenesis. |
| first_indexed | 2024-03-11T10:06:05Z |
| format | Article |
| id | doaj.art-a5c6b6502019479ca63f35fd7ada0666 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T10:06:05Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a5c6b6502019479ca63f35fd7ada06662023-11-16T15:03:08ZengMDPI AGCancers2072-66942022-12-0115121010.3390/cancers15010210Multi-Omics Analyses Identify Signatures in Patients with Liver Cirrhosis and Hepatocellular CarcinomaMing-Wei Lai0Yu-De Chu1Chao-Wei Hsu2Yi-Cheng Chen3Kung-Hao Liang4Chau-Ting Yeh5Department of Pediatrics, Chang Gung Memorial Hospital, Linkou Branch and Chang Gung University College of Medicine, Taoyuan 333, TaiwanLiver Research Center, Chang Gung Memorial Hospital, Linkou Branch and Chang Gung University College of Medicine, Taoyuan 333, TaiwanLiver Research Center, Chang Gung Memorial Hospital, Linkou Branch and Chang Gung University College of Medicine, Taoyuan 333, TaiwanDepartment of Hepatogastroenterology, Chang Gung Memorial Hospital, Linkou Branch and Chang Gung University College of Medicine, Taoyuan 333, TaiwanDepartment of Medical Research, Taipei Veterans General Hospital, Taipei 112, TaiwanLiver Research Center, Chang Gung Memorial Hospital, Linkou Branch and Chang Gung University College of Medicine, Taoyuan 333, TaiwanGut bacterial/viral dysbiosis, changes in circulating metabolites, and plasma cytokines/chemokines have been previously associated with various liver diseases. Here, we analyzed the associations between fecal microbial composition, circulating metabolites, and plasma cytokines/chemokines in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC). We recruited 10 HCC patients, 18 LC patients, and 17 healthy individuals. Their stool samples were used for gene sequencing of bacterial 16S rRNA and viral genomes, while plasma samples were utilized for the determination of endotoxin, zonulin, metabolite, and cytokine/chemokine levels. Dysbiosis was observed among gut bacteria and viruses, with significant changes in abundance at the genus and species levels, respectively. However, no differences were found between cohorts in the alpha and beta diversity. Plasma lipopolysaccharides and zonulin, but not trimethylamine N-oxide, were progressively increased in LC and HCC subjects. Profiling plasma metabolites and selected cytokines/chemokines revealed differential changes in the LC and HCC cohorts. Following joint correlation and correlation network analyses, regardless of etiology, common network signatures shared by LC and HCC patients were characterized by the gut virus Stenotrophomonas virus DLP5 and the uncultured Caudovirales phage, plasma metabolites pyruvic acid and acetic acid, and plasma cytokines/chemokines eotaxin and PDGF-AB/BB, respectively. Additionally, LC- and HCC-specific correlation networks were also identified. This study provides novel insights into altered gut microbial/viral composition that may contribute to pre-HCC disorders, metabolic reprogramming, or inflammatory microenvironments for hepatocarcinogenesis.https://www.mdpi.com/2072-6694/15/1/210microbiotaviromemetabolomicscytokine/chemokineliver cirrhosishepatocellular carcinoma |
| spellingShingle | Ming-Wei Lai Yu-De Chu Chao-Wei Hsu Yi-Cheng Chen Kung-Hao Liang Chau-Ting Yeh Multi-Omics Analyses Identify Signatures in Patients with Liver Cirrhosis and Hepatocellular Carcinoma Cancers microbiota virome metabolomics cytokine/chemokine liver cirrhosis hepatocellular carcinoma |
| title | Multi-Omics Analyses Identify Signatures in Patients with Liver Cirrhosis and Hepatocellular Carcinoma |
| title_full | Multi-Omics Analyses Identify Signatures in Patients with Liver Cirrhosis and Hepatocellular Carcinoma |
| title_fullStr | Multi-Omics Analyses Identify Signatures in Patients with Liver Cirrhosis and Hepatocellular Carcinoma |
| title_full_unstemmed | Multi-Omics Analyses Identify Signatures in Patients with Liver Cirrhosis and Hepatocellular Carcinoma |
| title_short | Multi-Omics Analyses Identify Signatures in Patients with Liver Cirrhosis and Hepatocellular Carcinoma |
| title_sort | multi omics analyses identify signatures in patients with liver cirrhosis and hepatocellular carcinoma |
| topic | microbiota virome metabolomics cytokine/chemokine liver cirrhosis hepatocellular carcinoma |
| url | https://www.mdpi.com/2072-6694/15/1/210 |
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