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

Study information

EditHistoryDelete

Mark reviewed

Your review change was submittedAdd a new Experiment

• Quality control
  • Retracted paper
  • Contamination issues suspected
  • Batch effect issues suspected
  • Uncontrolled confounding suspected
  • Results are suspect (various reasons)
  • Apply tags

    Tags applied

Needs review

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

39701092

DOI Digital object identifier for electronic documents.

10.4143/crt.2024.521

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

EditHistoryDelete

Mark reviewed

Your review change was submittedDuplicate this ExperimentAdd a new Signature

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

EditHistoryDelete

Mark reviewed

Your review change was submitted

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 Control	Links
Betaproteobacteria

Revision editor(s): Tosin

Signature 2

EditHistoryDelete

Mark reviewed

Your review change was submitted

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 Control	Links
Bacteroidia
Bacteroidota

Revision editor(s): Tosin

Experiment 2

EditHistoryDelete

Mark reviewed

Your review change was submittedDuplicate this ExperimentAdd a new Signature

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

EditHistoryDelete

Mark reviewed

Your review change was submitted

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 Control	Links
Alphaproteobacteria
Betaproteobacteria
Gammaproteobacteria
Pseudomonadota

Revision editor(s): Tosin

Signature 2

EditHistoryDelete

Mark reviewed

Your review change was submitted

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 Control	Links
Bacillota
Bacteroidia
Bacteroidota
Clostridia
Deinococci
Deinococcus_ThermusDeinococcus_Thermus

Revision editor(s): Tosin

Experiment 3

EditHistoryDelete

Mark reviewed

Your review change was submittedDuplicate this ExperimentAdd a new Signature

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

EditHistoryDelete

Mark reviewed

Your review change was submitted

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 Control	Links
Enterobacterales
Halomonadaceae
Halomonas
Mycobacteriaceae
Mycobacteriales
Mycobacterium
Oceanospirillales
Pseudomonadaceae
Pseudomonadales
Pseudomonas
Thermaceae
Thermales
Thermus

Revision editor(s): Tosin

Signature 2

EditHistoryDelete

Mark reviewed

Your review change was submitted

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 Control	Links
Aeromonadaceae
Aeromonadales
Aeromonas
Alloprevotella
Bacteroidaceae
Bacteroidales
Bacteroides
Eubacteriales
Lachnospiraceae
Prevotella
Prevotellaceae

Revision editor(s): Tosin

Experiment 4

EditHistoryDelete

Mark reviewed

Your review change was submittedDuplicate this ExperimentAdd a new Signature

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

EditHistoryDelete

Mark reviewed

Your review change was submitted

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 Control	Links
Lachnospiraceae
Oscillospiraceae
Ruminococcus
Roseburia
Lachnospira
Faecalibacterium

Revision editor(s): Tosin

Experiment 5

EditHistoryDelete

Mark reviewed

Your review change was submittedDuplicate this ExperimentAdd a new Signature

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

EditHistoryDelete

Mark reviewed

Your review change was submitted

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 Control	Links
Corynebacteriaceae
Corynebacterium
Enterobacter
Enterobacteriaceae
Mycobacteriaceae
Mycobacterium
Pseudomonadaceae
Pseudomonas

Revision editor(s): Tosin