Relationships between the Microbiome and Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

From BugSigDB
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Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Lee HI, Jang BS, Chang JH, Kim E, Lee TH, Park JH, Chie EK
Journal
Cancer research and treatment
Year
2024
Keywords:
Butyrates, Chemoradiotherapy, Microbiota, Rectal neoplasms, Response prediction model
PURPOSE: This study aimed to investigate the dynamic changes in the microbiome of patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (nCRT), focusing on the relationship between the microbiome and response to nCRT. MATERIALS AND METHODS: We conducted a longitudinal study involving 103 samples from 26 patients with LARC. Samples were collected from both the tumor and normal rectal tissues before and after nCRT. Diversity, taxonomic, and network analyses were performed to compare the microbiome profiles across different tissue types, pre- and post-nCRT time-points, and nCRT responses. RESULTS: Between the tumor and normal tissue samples, no differences in microbial diversity and composition were observed. However, when pre- and post-nCRT samples were compared, there was a significant decrease in diversity, along with notable changes in composition. Non-responders exhibited more extensive changes in their microbiome composition during nCRT, characterized by an increase in pathogenic microbes. Meanwhile, responders had relatively stable microbiome communities with more enriched butyrate-producing bacteria. Network analysis revealed distinct patterns of microbial interactions between responders and non-responders, where butyrate-producing bacteria formed strong networks in responders, while opportunistic pathogens formed strong networks in non-responders. A Bayesian network model for predicting the nCRT response was established, with butyrate-producing bacteria playing a major predictive role. CONCLUSION: Our study demonstrated a significant association between the microbiome and nCRT response in LARC patients, leading to the development of a microbiome-based response prediction model. These findings suggest potential applications of microbiome signatures for predicting and optimizing nCRT treatment in LARC patients.

Experiment 1


Needs review

Curated date: 2025/05/07

Curator: Tosin

Revision editor(s): Tosin

Subjects

Location of subjects
South Korea
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
Rectum Intestinum rectum,Rectal sac,Terminal portion of intestine,Terminal portion of large intestine,Rectum,rectum
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Response to platinum-based neoadjuvant chemotherapy Response to platinum-based neoadjuvant chemotherapy,response to platinum-based neoadjuvant chemotherapy
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Pre-nCRT (Pre-neoadjuvant chemoradiotherapy) responders
Group 1 name Corresponds to the case (exposed) group for case-control studies
Post-nCRT (Post-neoadjuvant chemoradiotherapy) responders
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients who responded post-neoadjuvant chemoradiotherapy
Group 0 sample size Number of subjects in the control (unexposed) group
9
Group 1 sample size Number of subjects in the case (exposed) group
9
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
1 month

Lab analysis

16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
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
LEfSe
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
1
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
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
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
decreased
Richness Number of species
decreased

Signature 1

Needs review

Curated date: 2025/05/07

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 3A

Description: Cladogram of differentially abundant taxa before and after nCRT (Neo-adjuvant chemoradiotherapy) in responders

Abundance in Group 1: increased abundance in Post-nCRT (Post-neoadjuvant chemoradiotherapy) responders

NCBI Quality ControlLinks
Betaproteobacteria

Revision editor(s): Tosin

Signature 2

Needs review

Curated date: 2025/05/07

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 3A

Description: Cladogram of differentially abundant taxa before and after nCRT (Neo-adjuvant chemoradiotherapy) in responders

Abundance in Group 1: decreased abundance in Post-nCRT (Post-neoadjuvant chemoradiotherapy) responders

NCBI Quality ControlLinks
Bacteroidia
Bacteroidota

Revision editor(s): Tosin

Experiment 2


Needs review

Curated date: 2025/05/07

Curator: Tosin

Revision editor(s): Tosin

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Pre-nCRT (Pre-neoadjuvant chemoradiotherapy) non- responders
Group 1 name Corresponds to the case (exposed) group for case-control studies
Post-nCRT (Post-neoadjuvant chemoradiotherapy) non- responders
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients who did not respond, post-neoadjuvant chemoradiotherapy
Group 0 sample size Number of subjects in the control (unexposed) group
17
Group 1 sample size Number of subjects in the case (exposed) group
17

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
decreased
Richness Number of species
decreased

Signature 1

Needs review

Curated date: 2025/05/07

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 3A

Description: Cladogram of differentially abundant taxa before and after nCRT (Neo-adjuvant chemoradiotherapy) in non-responders

Abundance in Group 1: increased abundance in Post-nCRT (Post-neoadjuvant chemoradiotherapy) non- responders

NCBI Quality ControlLinks
Alphaproteobacteria
Betaproteobacteria
Gammaproteobacteria
Pseudomonadota

Revision editor(s): Tosin

Signature 2

Needs review

Curated date: 2025/05/07

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 3A

Description: Cladogram of differentially abundant taxa before and after nCRT (Neo-adjuvant chemoradiotherapy) in non-responders

Abundance in Group 1: decreased abundance in Post-nCRT (Post-neoadjuvant chemoradiotherapy) non- responders

NCBI Quality ControlLinks
Bacillota
Bacteroidia
Bacteroidota
Clostridia
Deinococci
Deinococcus_ThermusDeinococcus_Thermus

Revision editor(s): Tosin

Experiment 3


Needs review

Curated date: 2025/05/07

Curator: Tosin

Revision editor(s): Tosin

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Pre-nCRT (Pre-neoadjuvant chemoradiotherapy)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Post-nCRT (Post-neoadjuvant chemoradiotherapy)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients during post-neoadjuvant chemoradiotherapy
Group 0 sample size Number of subjects in the control (unexposed) group
26
Group 1 sample size Number of subjects in the case (exposed) group
26

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
decreased
Richness Number of species
decreased

Signature 1

Needs review

Curated date: 2025/05/07

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 3A

Description: Differentially abundant taxa before and after nCRT: red nodes indicate increased abundance post-nCRT; green nodes show decreased abundance

Abundance in Group 1: increased abundance in Post-nCRT (Post-neoadjuvant chemoradiotherapy)

NCBI Quality ControlLinks
Enterobacterales
Halomonadaceae
Halomonas
Mycobacteriaceae
Mycobacteriales
Mycobacterium
Oceanospirillales
Pseudomonadaceae
Pseudomonadales
Pseudomonas
Thermaceae
Thermales
Thermus

Revision editor(s): Tosin

Signature 2

Needs review

Curated date: 2025/05/07

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 3A

Description: Differentially abundant taxa before and after nCRT (Neo-adjuvant chemoradiotherapy) : red nodes indicate increased abundance post-nCRT (Neo-adjuvant chemoradiotherapy) : green nodes show decreased abundance

Abundance in Group 1: decreased abundance in Post-nCRT (Post-neoadjuvant chemoradiotherapy)

NCBI Quality ControlLinks
Aeromonadaceae
Aeromonadales
Aeromonas
Alloprevotella
Bacteroidaceae
Bacteroidales
Bacteroides
Eubacteriales
Lachnospiraceae
Prevotella
Prevotellaceae

Revision editor(s): Tosin

Experiment 4


Needs review

Curated date: 2025/05/07

Curator: Tosin

Revision editor(s): Tosin

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Pre-nCRT (Pre-neoadjuvant chemoradiotherapy) Non-responders
Group 1 name Corresponds to the case (exposed) group for case-control studies
Pre-nCRT (Pre-neoadjuvant chemoradiotherapy) Responders
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer within Pre-nCRT (Pre-neoadjuvant chemoradiotherapy) samples
Group 0 sample size Number of subjects in the control (unexposed) group
17
Group 1 sample size Number of subjects in the case (exposed) group
9

Lab analysis

Statistical Analysis

Statistical test
ANOVA
T-Test
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified


Signature 1

Needs review

Curated date: 2025/05/07

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 3B and 3C

Description: Heatmap and relative abundance of pre-nCRT (pre-neoadjuvant chemoradiotherapy) microbiome composition at family and genera level. R, responder; NR, non-responder.

Abundance in Group 1: increased abundance in Pre-nCRT (Pre-neoadjuvant chemoradiotherapy) Responders

NCBI Quality ControlLinks
Lachnospiraceae
Oscillospiraceae
Ruminococcus
Roseburia
Lachnospira
Faecalibacterium

Revision editor(s): Tosin

Experiment 5


Needs review

Curated date: 2025/05/07

Curator: Tosin

Revision editor(s): Tosin

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Post-nCRT (Post-neoadjuvant chemoradiotherapy) Non-responders
Group 1 name Corresponds to the case (exposed) group for case-control studies
Post-nCRT (Post-neoadjuvant chemoradiotherapy) Responders
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients during Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer within Post-nCRT (Post-neoadjuvant chemoradiotherapy) samples

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/05/07

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 3D and 3E

Description: Heatmap and relative abundance of post-nCRT (post-neoadjuvant chemoradiotherapy) microbiome composition at family and genera level. R, responder; NR, non-responder.

Abundance in Group 1: decreased abundance in Post-nCRT (Post-neoadjuvant chemoradiotherapy) Responders

NCBI Quality ControlLinks
Corynebacteriaceae
Corynebacterium
Enterobacter
Enterobacteriaceae
Mycobacteriaceae
Mycobacterium
Pseudomonadaceae
Pseudomonas

Revision editor(s): Tosin