Gut microbiota composition in chemotherapy and targeted therapy of patients with metastatic colorectal cancer

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Reviewed Marked as Reviewed by Svetlana up on 2025-3-26
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Chen YC, Chuang CH, Miao ZF, Yip KL, Liu CJ, Li LH, Wu DC, Cheng TL, Lin CY, Wang JY
Journal
Frontiers in oncology
Year
2022
Keywords:
Bifidobacterium species, Fusobacterium nucleatum, Klebsiella quasipneumoniae, Lactobacillus species, metastatic colorectal cancer, targeted therapy
Studies have reported the effects of the gut microbiota on colorectal cancer (CRC) chemotherapy, but few studies have investigated the association between gut microbiota and targeted therapy. This study investigated the role of the gut microbiota in the treatment outcomes of patients with metastatic CRC (mCRC). We enrolled 110 patients with mCRC and treated them with standard cancer therapy. Stool samples were collected before administering a combination of chemotherapy and targeted therapy. Patients who had a progressive disease (PD) or partial response (PR) for at least 12 cycles of therapy were included in the study. We further divided these patients into anti-epidermal growth factor receptor (cetuximab) and anti-vascular endothelial growth factor (bevacizumab) subgroups. The gut microbiota of the PR group and bevacizumab-PR subgroup exhibited significantly higher α-diversity. The β-diversity of bacterial species significantly differed between the bevacizumab-PR and bevacizumab-PD groups (P = 0.029). Klebsiella quasipneumoniae exhibited the greatest fold change in abundance in the PD group than in the PR group. Lactobacillus and Bifidobacterium species exhibited higher abundance in the PD group. The abundance of Fusobacterium nucleatum was approximately 32 times higher in the PD group than in the PR group. A higher gut microbiota diversity was associated with more favorable treatment outcomes in the patients with mCRC. Bacterial species analysis of stool samples yielded heterogenous results. K. quasipneumoniae exhibited the greatest fold change in abundance among all bacterial species in the PD group. This result warrants further investigation especially in a Taiwanese population.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2025-3-26

Curated date: 2025/03/24

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Subjects

Location of subjects
Taiwan
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
Treatment outcome measurement Treatment outcome measurement,treatment outcome measurement
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Partial response group- PR
Group 1 name Corresponds to the case (exposed) group for case-control studies
Progressive disease group- PD
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients who had a progressive disease (PD) for at least 12 cycles of therapy
Group 0 sample size Number of subjects in the control (unexposed) group
31
Group 1 sample size Number of subjects in the case (exposed) group
24

Lab analysis

Sequencing type
WMS
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).
raw counts
Statistical test
DESeq2
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)?
Yes

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-3-26

Curated date: 2025/03/24

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4A

Description: Results of the log2 fold change in the disease progression and partial response groups

Abundance in Group 1: increased abundance in Progressive disease group- PD

NCBI Quality ControlLinks
Veillonella orientalis
Veillonella nakazawae
Veillonella dispar
Veillonella atypica
Streptococcus sp. HSISS3
Limosilactobacillus vaginalis
Limosilactobacillus mucosae
Ligilactobacillus salivarius
Lactobacillus crispatus
Lacticaseibacillus paracasei
Klebsiella quasipneumoniae
Fusobacterium nucleatum
Bifidobacterium dentium
Bifidobacterium breve
Bifidobacterium bifidum

Revision editor(s): Miss Lulu

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-3-26

Curated date: 2025/03/24

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4A

Description: Results of the log2 fold change in the disease progression and partial response groups

Abundance in Group 1: decreased abundance in Progressive disease group- PD

NCBI Quality ControlLinks
Prevotella dentalis
Segatella copri
Phascolarctobacterium sp. Marseille-Q4147
Klebsiella aerogenes
Fusobacterium mortiferum
Desulfovibrio fairfieldensis
Adlercreutzia equolifaciens

Revision editor(s): Miss Lulu

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2025-3-26

Curated date: 2025/03/24

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Bevacizumab-PR subgroup
Group 1 name Corresponds to the case (exposed) group for case-control studies
Bevacizumab-PD subgroup
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with progressive disease (PD) who had anti-vascular endothelial growth factor (bevacizumab) subgroups.
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
18

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-3-26

Curated date: 2025/03/24

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4B

Description: Results of the log2 fold change in the subgroups of bevacizumab

Abundance in Group 1: increased abundance in Bevacizumab-PD subgroup

NCBI Quality ControlLinks
Akkermansia muciniphila
Anaerostipes caccae
Bifidobacterium breve
Bifidobacterium dentium
Enterococcus avium
Enterococcus sp. FDAARGOS_553
Fusobacterium nucleatum
Haemophilus influenzae
Lacticaseibacillus paracasei
Lactobacillus delbrueckii
Limosilactobacillus fermentum
Morganella morganii
Sutterella wadsworthensis
Veillonella atypica
Limosilactobacillus vaginalis

Revision editor(s): Miss Lulu

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-3-26

Curated date: 2025/03/24

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4B

Description: Results of the log2 fold change in the subgroups of bevacizumab

Abundance in Group 1: decreased abundance in Bevacizumab-PD subgroup

NCBI Quality ControlLinks
Segatella copri
Prevotella dentalis
Phocaeicola coprophilus

Revision editor(s): Miss Lulu

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2025-3-26

Curated date: 2025/03/24

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Cetuximab-PR subgroup
Group 1 name Corresponds to the case (exposed) group for case-control studies
Cetuximab-PD subgroup
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with progressive disease (PD) who had anti-epidermal growth factor receptor (cetuximab) subgroups.
Group 0 sample size Number of subjects in the control (unexposed) group
14
Group 1 sample size Number of subjects in the case (exposed) group
6

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-3-26

Curated date: 2025/03/24

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4C

Description: Results of the log2 fold change in the subgroups of cetuximab

Abundance in Group 1: increased abundance in Cetuximab-PD subgroup

NCBI Quality ControlLinks
Anaerostipes caccae
Adlercreutzia equolifaciens

Revision editor(s): Miss Lulu