Gut bacteria identified in colorectal cancer patients promote tumourigenesis via butyrate secretion

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/10

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

34584098

DOI Digital object identifier for electronic documents.

10.1038/s41467-021-25965-x

URI

Authors

Okumura S, Konishi Y, Narukawa M, Sugiura Y, Yoshimoto S, Arai Y, Sato S, Yoshida Y, Tsuji S, Uemura K, Wakita M, Matsudaira T, Matsumoto T, Kawamoto S, Takahashi A, Itatani Y, Miki H, Takamatsu M, Obama K, Takeuchi K, Suematsu M, Ohtani N, Fukunaga Y, Ueno M, Sakai Y, Nagayama S, Hara E

Journal

Nature communications

Year

2021

Emerging evidence is revealing that alterations in gut microbiota are associated with colorectal cancer (CRC). However, very little is currently known about whether and how gut microbiota alterations are causally associated with CRC development. Here we show that 12 faecal bacterial taxa are enriched in CRC patients in two independent cohort studies. Among them, 2 Porphyromonas species are capable of inducing cellular senescence, an oncogenic stress response, through the secretion of the bacterial metabolite, butyrate. Notably, the invasion of these bacteria is observed in the CRC tissues, coinciding with the elevation of butyrate levels and signs of senescence-associated inflammatory phenotypes. Moreover, although the administration of these bacteria into ApcΔ14/+ mice accelerate the onset of colorectal tumours, this is not the case when bacterial butyrate-synthesis genes are disrupted. These results suggest a causal relationship between Porphyromonas species overgrowth and colorectal tumourigenesis which may be due to butyrate-induced senescence.

Experiment 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/10

Curated date: 2022/06/05

Curator: Jeshudy

Revision editor(s): WikiWorks, Claregrieve1, Jeshudy, Victoria, Ifeanyisam

Differences from previous experiment shown

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: 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: Colorectal cancer cancer of colorectum,cancer of large bowel,cancer of large intestine,cancer of the large bowel,colon cancer,colorectal cancer,colorectum cancer,CRC,large intestine cancer,malignant colorectal neoplasm,malignant colorectal tumor,malignant colorectum neoplasm,malignant large bowel neoplasm,malignant large bowel tumor,malignant large intestine neoplasm,malignant large intestine tumor,malignant neoplasm of colorectum,malignant neoplasm of large bowel,malignant neoplasm of large intestine,malignant neoplasm of the large bowel,malignant neoplasm of the large intestine,malignant tumor of large bowel,malignant tumor of large intestine,malignant tumor of the large bowel,malignant tumor of the large intestine,Colorectal cancer

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Healthy Individuals

Group 1 name Corresponds to the case (exposed) group for case-control studies: Patients with early CRC

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients with early colorectal cancer

Group 0 sample size Number of subjects in the control (unexposed) group: 129

Group 1 sample size Number of subjects in the case (exposed) group: 136

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

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V1-V2

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: Kruskall-Wallis; 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)?: Yes

Signature 1

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Source: Figure 1B

Description: Differential microbial abundance between early CRC patients and healthy controls

Abundance in Group 1: increased abundance in Patients with early CRC

NCBI	Quality Control	Links
Fusobacterium nucleatum
Gemella morbillorum
Peptostreptococcus stomatis

Revision editor(s): Jeshudy, Claregrieve1, WikiWorks

Experiment 3

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Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/10

Curated date: 2022/06/05

Curator: Jeshudy

Revision editor(s): WikiWorks, Claregrieve1, Jeshudy, Victoria, Ifeanyisam

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Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies: Patients with advanced CRC

Group 1 sample size Number of subjects in the case (exposed) group: 153

Statistical Analysis

Signature 1

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Source: Figure 1B

Description: Differential microbial abundance between advanced CRC patients and healthy controls

Abundance in Group 1: increased abundance in Patients with advanced CRC

NCBI	Quality Control	Links
Alloprevotella tannerae
Dialister pneumosintes
Fusobacterium nucleatum
Gemella morbillorum
Parvimonas micra
Peptostreptococcus anaerobius
Peptostreptococcus stomatis
Porphyromonas asaccharolytica
Porphyromonas gingivalis
Prevotella intermedia
Solobacterium moorei

Revision editor(s): Jeshudy, Claregrieve1, WikiWorks

Experiment 4

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Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/10

Curated date: 2022/06/05

Curator: Jeshudy

Revision editor(s): WikiWorks, Claregrieve1, Jeshudy, ChiomaBlessing, Victoria, Ifeanyisam

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Surgical resection Surgical resection,surgical resection

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Before resection

Group 1 name Corresponds to the case (exposed) group for case-control studies: After resection

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients post surgical resection of Cohort-1 CRC specimens

Group 0 sample size Number of subjects in the control (unexposed) group: 380

Group 1 sample size Number of subjects in the case (exposed) group: 380

Statistical Analysis

Statistical test: Mann-Whitney (Wilcoxon)