Distinct alterations of gut microbiota between viral- and non-viral-related hepatocellular carcinoma
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Jinato T, Anuntakarun S, Satthawiwat N, Chuaypen N, Tangkijvanich P
Journal
Applied microbiology and biotechnology
Year
2024
Keywords:
16 s rRNA, Biomarker, Gut dysbiosis, HCC, NAFLD, Viral hepatitis
Altered gut microbiota has been connected to hepatocellular carcinoma (HCC) occurrence and advancement. This study was conducted to identify a gut microbiota signature in differentiating between viral-related HCC (Viral-HCC) and non-hepatitis B-, non-hepatitis C-related HCC (NBNC-HCC). Fecal specimens were obtained from 16 healthy controls, 33 patients with viral-HCC (17 and 16 cases with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, respectively), and 18 patients with NBNC-HCC. Compositions of fecal microbiota were assessed by 16S rRNA sequencing. Bioinformatic analysis was performed by the DADA2 pipeline in the R program. Significantly different genera from the top 50 relative abundance were used to classify between subgroups of HCC by the Random Forest algorithm. Our data demonstrated that the HCC group had a significantly decreased alpha-diversity and changed microbial composition in comparison with healthy controls. Within the top 50 relative abundance, there were 11 genera including Faecalibacterium, Agathobacter, and Coprococcus that were significantly enhanced in Viral-HCC, while 5 genera such as Bacteroides, Streptococcus, Ruminococcus gnavus group, Parabacteroides, and Erysipelatoclostridium were enhanced in NBNC-HCC. Compared to Viral-HCC, the NBNC-HCC subgroup significantly reduced various short-chain fatty acid-producing bacteria, as well as declined fecal butyrate but elevated plasma surrogate markers of microbial translocation. Based on the machine learning algorithm, a high diagnostic accuracy to classify HCC subgroups was achieved with an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.94. Collectively, these data revealed that gut dysbiosis was distinct according to etiological factors of HCC, which might play an essential role in hepatocarcinogenesis. These findings underscore the possible use of a gut microbiota signature for the diagnosis and therapeutic approaches regarding different subgroups of HCC. KEY POINTS: • Gut dysbiosis is connected to hepatocarcinogenesis and can be used as a novel biomarker. • Gut microbiota composition is significantly altered in different etiological factors of HCC. • Microbiota-based signature can accurately distinguish between Viral-HCC and NBNC-HCC.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2024-6-11
Subjects
- Location of subjects
- Thailand
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Hepatocellular carcinoma adult hepatoma,adult primary hepatocellular carcinoma,cancer, hepatocellular,carcinoma of liver,carcinoma of liver cells,carcinoma of the liver cells,carcinoma, hepatocellular, malignant,HCC,hepatoblastoma,hepatoblastoma caused by somatic mutation,hepatocellular adenocarcinoma,hepatocellular cancer,hepatocellular carcinoma,hepatoma,liver and intrahepatic bile duct carcinoma,liver cancer,liver carcinoma,liver cell cancer (hepatocellular carcinoma),liver cell carcinoma,primary carcinoma of liver cells,primary carcinoma of the liver cells,Hepatocellular carcinoma
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Patients with Hepatocellular carcinoma (HCC)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- patients with viral related hepatocellular carcinoma or non-hepatitis B-, non-hepatitis C-related hepatocellular carcinoma whose diagnosis of HCC was documented by dynamic computed tomography (CT) and/or magnetic resonance imaging (MRI) regarding the clinical guideline of the American Association for the Study of Liver Diseases (AASLD)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 16
- Group 1 sample size Number of subjects in the case (exposed) group
- 51
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- within 2 weeks of fecal sample collection
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-V4
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- Mann-Whitney (Wilcoxon)
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-6-11
Source: Table 2
Description: The significant taxa from the top 50 relative abundance genus level compared between healthy controls and Hepatocellular carcinoma patients.
Abundance in Group 1: increased abundance in Patients with Hepatocellular carcinoma (HCC)
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides | ||
| Streptococcus | ||
| Mediterraneibacter gnavus | ||
| Veillonella | ||
| Thomasclavelia |
Revision editor(s): Idiaru angela
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-6-11
Source: Table 2
Description: The significant taxa from the top 50 relative abundance genus level compared between healthy controls and Hepatocellular carcinoma patients.
Abundance in Group 1: decreased abundance in Patients with Hepatocellular carcinoma (HCC)
Revision editor(s): Idiaru angela
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2024-6-11
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Hepatitis virus-related hepatocellular carcinoma hepatitis virus-related hepatocellular cancer,Hepatitis virus-related hepatocellular carcinoma,hepatitis virus-related hepatocellular carcinoma
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- viral-related Hepatocellular carcinoma
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- non-hepatitis B-, non-hepatitis C-related Hepatocellular carcinoma
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with non-hepatitis B-, non-hepatitis C-related Hepatocellular carcinoma whose diagnosis of HCC was documented by dynamic computed tomography (CT) and/or magnetic resonance imaging (MRI) regarding the clinical guideline of the American Association for the Study of Liver Diseases (AASLD)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 33
- Group 1 sample size Number of subjects in the case (exposed) group
- 18
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-6-11
Source: Table 3
Description: The significant taxa from the top 50 relative abundance genus level compared between Viral- and NBNC-HCC
Abundance in Group 1: increased abundance in non-hepatitis B-, non-hepatitis C-related Hepatocellular carcinoma
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides | ||
| Streptococcus | ||
| Mediterraneibacter gnavus | ||
| Parabacteroides | ||
| Thomasclavelia |
Revision editor(s): Idiaru angela
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-6-11
Source: Table 3
Description: The significant taxa from the top 50 relative abundance genus level compared between Viral- and NBNC-HCC
Abundance in Group 1: decreased abundance in non-hepatitis B-, non-hepatitis C-related Hepatocellular carcinoma
Revision editor(s): Idiaru angela
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2024-6-11
Differences from previous experiment shown
Subjects
Lab analysis
Statistical Analysis
- Statistical test
- LEfSe
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-6-11
Source: Figure 4B
Description: LEfSe identifies the microbiota that differed the most between NBNC-HCC and Viral-HCC
Abundance in Group 1: increased abundance in non-hepatitis B-, non-hepatitis C-related Hepatocellular carcinoma
| NCBI | Quality Control | Links |
|---|---|---|
| Clostridiaceae | ||
| Eubacteriales | ||
| Oscillospiraceae | ||
| UBA1819UBA1819 | ||
| Lactobacillales | ||
| Carnobacteriaceae | ||
| Granulicatella | ||
| Bacillota | ||
| Peptostreptococcaceae |
Revision editor(s): Idiaru angela
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-6-11
Source: Figure 4B
Description: LEfSe identifies the microbiota that differed the most between NBNC-HCC and Viral-HCC
Abundance in Group 1: decreased abundance in non-hepatitis B-, non-hepatitis C-related Hepatocellular carcinoma
| NCBI | Quality Control | Links |
|---|---|---|
| Lachnospirales | ||
| Lachnospiraceae | ||
| Bacteroidota | ||
| Bacteroidia | ||
| Bacteroidales | ||
| Prevotellaceae |
Revision editor(s): Idiaru angela
Experiment 4
Reviewed Marked as Reviewed by Svetlana up on 2024-6-11
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Hepatocellular carcinoma adult hepatoma,adult primary hepatocellular carcinoma,cancer, hepatocellular,carcinoma of liver,carcinoma of liver cells,carcinoma of the liver cells,carcinoma, hepatocellular, malignant,HCC,hepatoblastoma,hepatoblastoma caused by somatic mutation,hepatocellular adenocarcinoma,hepatocellular cancer,hepatocellular carcinoma,hepatoma,liver and intrahepatic bile duct carcinoma,liver cancer,liver carcinoma,liver cell cancer (hepatocellular carcinoma),liver cell carcinoma,primary carcinoma of liver cells,primary carcinoma of the liver cells,Hepatocellular carcinoma
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy controls
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with non-hepatitis B-, non-hepatitis C-related Hepatocellular carcinoma whose diagnosis of HCC was documented by dynamic computed tomography (CT) and/or magnetic resonance imaging (MRI) regarding the clinical guideline of the American Association for the Study of Liver Diseases (AASLD)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 16
Lab analysis
Statistical Analysis
- Statistical test
- Not specified
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Not specified
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- Not specified
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Experiment 5
Reviewed Marked as Reviewed by Svetlana up on 2024-6-11
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Hepatitis virus-related hepatocellular carcinoma hepatitis virus-related hepatocellular cancer,Hepatitis virus-related hepatocellular carcinoma,hepatitis virus-related hepatocellular carcinoma
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Hepatitis-B virus related Hepatocellular carcinoma
- Group 0 sample size Number of subjects in the control (unexposed) group
- 17
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
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