Gallbladder microbiota composition is associated with pancreaticobiliary and gallbladder cancer prognosis

From BugSigDB
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-22
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Kirishima M, Yokoyama S, Matsuo K, Hamada T, Shimokawa M, Akahane T, Sugimoto T, Tsurumaru H, Ishibashi M, Mataki Y, Ootsuka T, Nomoto M, Hayashi C, Horiguchi A, Higashi M, Tanimoto A
Journal
BMC microbiology
Year
2022
Keywords:
Alpha diversity, Beta diversity, Bile, Biomarker, Cancer, Gallbladder, Microbiota, Overall survival, Pancreaticobiliary tract, Prognosis
BACKGROUND: The microbial population of the intestinal tract and its relationship to specific diseases has been extensively studied during the past decade. However, reports characterizing the bile microbiota are rare. This study aims to investigate the microbiota composition in patients with pancreaticobiliary cancers and benign diseases by 16S rRNA gene amplicon sequencing and to evaluate its potential value as a biomarker for the cancer of the bile duct, pancreas, and gallbladder. RESULTS: We enrolled patients who were diagnosed with cancer, cystic lesions, and inflammation of the pancreaticobiliary tract. The study cohort comprised 244 patients. We extracted microbiome-derived DNA from the bile juice in surgically resected gallbladders. The microbiome composition was not significantly different according to lesion position and cancer type in terms of alpha and beta diversity. We found a significant difference in the relative abundance of Campylobacter, Citrobacter, Leptotrichia, Enterobacter, Hungatella, Mycolicibacterium, Phyllobacterium and Sphingomonas between patients without and with lymph node metastasis. CONCLUSIONS: There was a significant association between the relative abundance of certain microbes and overall survival prognosis. These microbes showed association with good prognosis in cholangiocarcinoma, but with poor prognosis in pancreatic adenocarcinoma, and vice versa. Our findings suggest that pancreaticobiliary tract cancer patients have an altered microbiome composition, which might be a biomarker for distinguishing malignancy.

Experiment 1


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-22

Curated date: 2023/10/30

Curator: Folakunmi

Revision editor(s): Folakunmi

Subjects

Location of subjects
Japan
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
Bile Fel,Gall,Bile,bile
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Disease progression measurement Disease progression measurement,disease progression measurement
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Early cholangiocarcinoma
Group 1 name Corresponds to the case (exposed) group for case-control studies
Advanced cholangiocarcinoma
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with lymph node metastasis in cholangiocarcinoma, where lymph node metastasis denotes advanced stage and the absence of lymph node metastasis denotes early stage.
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
none

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

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-22

Curated date: 2023/10/30

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: Table 2

Description: Patients with lymph node metastasis in cholangiocarcinoma, where lymph node metastasis denotes advanced stage and the absence of lymph node metastasis denotes early stage.

Abundance in Group 1: increased abundance in Advanced cholangiocarcinoma

NCBI Quality ControlLinks
Campylobacter
Citrobacter
Leptotrichia

Revision editor(s): Folakunmi

Experiment 2


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-22

Curated date: 2023/10/30

Curator: Folakunmi

Revision editor(s): Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Early pancreatic ductal adenocarcinoma
Group 1 name Corresponds to the case (exposed) group for case-control studies
Advanced pancreatic ductal adenocarcinoma
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with lymph node metastasis in pancreatic ductal adenocarcinoma (PDAC), where lymph node metastasis denotes advanced stage and the absence of lymph node metastasis denotes early stage.

Lab analysis

Statistical Analysis

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-22

Curated date: 2023/10/30

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: Table 2

Description: Patients with lymph node metastasis in pancreatic ductal adenocarcinoma (PDAC), where lymph node metastasis denotes advanced stage and the absence of lymph node metastasis denotes early stage.

Abundance in Group 1: increased abundance in Advanced pancreatic ductal adenocarcinoma

NCBI Quality ControlLinks
Phyllobacterium
Sphingomonas

Revision editor(s): Folakunmi

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-22

Curated date: 2023/10/30

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: Table 2

Description: Patients with lymph node metastasis in pancreatic ductal adenocarcinoma (PDAC), where lymph node metastasis denotes advanced stage and the absence of lymph node metastasis denotes early stage.

Abundance in Group 1: decreased abundance in Advanced pancreatic ductal adenocarcinoma

NCBI Quality ControlLinks
Enterobacter
Hungatella
Mycobacterium

Revision editor(s): Folakunmi

Experiment 3


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-22

Curated date: 2023/10/30

Curator: Folakunmi

Revision editor(s): Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
intraductal papillary mucinous neoplasm (IPMN)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Intraductal papillary mucinous carcinoma (IPMC)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Intraductal papillary mucinous carcinoma (IPMC) in pancreas cystic lesions.
Group 0 sample size Number of subjects in the control (unexposed) group
20
Group 1 sample size Number of subjects in the case (exposed) group
10

Lab analysis

Statistical Analysis

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-22

Curated date: 2023/10/30

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: Table 2

Description: Abundant taxa in Intraductal papillary mucinous carcinoma (IPMC) when compared to intraductal papillary mucinous neoplasm.

Abundance in Group 1: increased abundance in Intraductal papillary mucinous carcinoma (IPMC)

NCBI Quality ControlLinks
Actinomyces
Alloprevotella
Bilophila
Dialister
Eggerthella
Selenomonas
Streptococcus

Revision editor(s): Folakunmi

Experiment 4


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-22

Curated date: 2023/10/30

Curator: Folakunmi

Revision editor(s): Folakunmi

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Disease prognosis measurement Disease prognosis measurement,disease prognosis measurement
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Poor prognosis in bile duct lesion cases
Group 1 name Corresponds to the case (exposed) group for case-control studies
Good prognosis in bile duct lesion cases
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The group with good prognostic factors after adjustment for clinicopathologic variables ( sex, age, ASA score, stages, and the administration of preoperative chemotherapy) in bile duct lesion cases. These clinical conditions were found to be non-confounding.
Group 0 sample size Number of subjects in the control (unexposed) group
101
Group 1 sample size Number of subjects in the case (exposed) group
101

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
raw counts
Statistical test
Cox Proportional-Hazards Regression

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
unchanged
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-22

Curated date: 2023/11/06

Curator: Folakunmi

Revision editor(s): Folakunmi, ChiomaBlessing

Source: Table 4 + Results within text (Page 4, under subheading - "Evaluation of threshold value of individual microbiota relative abundance for prognosis")

Description: Differentially abundant taxa between poor prognosis and good prognosis in bile duct lesion cases using Cox proportional hazards model analysis.

Abundance in Group 1: increased abundance in Good prognosis in bile duct lesion cases

NCBI Quality ControlLinks
Fusobacterium
Streptococcus
Veillonella

Revision editor(s): Folakunmi, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-22

Curated date: 2023/11/06

Curator: Folakunmi

Revision editor(s): Folakunmi, ChiomaBlessing

Source: Table 4 + Results within text (Page 4, under subheading - "Evaluation of threshold value of individual microbiota relative abundance for prognosis")

Description: Differentially abundant taxa between poor prognosis and good prognosis in bile duct lesion cases using Cox proportional hazards model analysis.

Abundance in Group 1: decreased abundance in Good prognosis in bile duct lesion cases

NCBI Quality ControlLinks
Bacteroides
Corynebacterium
Enterococcus
Haemophilus
Hungatella
Lawsonella
Moraxella
Staphylococcus

Revision editor(s): Folakunmi, ChiomaBlessing

Experiment 5


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-22

Curated date: 2023/11/06

Curator: Folakunmi

Revision editor(s): Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Poor prognosis in pancreatic lesion cases
Group 1 name Corresponds to the case (exposed) group for case-control studies
Good prognosis in pancreatic lesion cases
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The group with good prognostic factors after adjustment for clinicopathologic variables ( sex, age, ASA score, stages, and the administration of preoperative chemotherapy) in pancreatic lesion cases. These clinicopathologic variables were found to be non-confounding.
Group 0 sample size Number of subjects in the control (unexposed) group
112
Group 1 sample size Number of subjects in the case (exposed) group
112

Lab analysis

Statistical Analysis

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
unchanged
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-22

Curated date: 2023/11/06

Curator: Folakunmi

Revision editor(s): Folakunmi, ChiomaBlessing

Source: Table 4 + Results within text (Page 5, under subheading - "Evaluation of threshold value of individual microbiota relative abundance for prognosis")

Description: Differentially abundant taxa between poor prognosis and good prognosis in pancreatic lesion cases using Cox proportional hazards model analysis.

Abundance in Group 1: increased abundance in Good prognosis in pancreatic lesion cases

NCBI Quality ControlLinks
Bacteroides
Enterococcus
Raoultella
Staphylococcus
Streptococcus

Revision editor(s): Folakunmi, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-22

Curated date: 2023/11/06

Curator: Folakunmi

Revision editor(s): Folakunmi, ChiomaBlessing

Source: Table 4 + Results within text (Page 5, under subheading - "Evaluation of threshold value of individual microbiota relative abundance for prognosis")

Description: Differentially abundant taxa between poor prognosis and good prognosis in pancreatic lesion cases using Cox proportional hazards model analysis.

Abundance in Group 1: decreased abundance in Good prognosis in pancreatic lesion cases

NCBI Quality ControlLinks
Acinetobacter
Klebsiella
Paracoccus
Selenomonas
Veillonella

Revision editor(s): Folakunmi, ChiomaBlessing