Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer

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Reviewed Marked as Reviewed by Atrayees on 2023-8-7
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Yachida S, Mizutani S, Shiroma H, Shiba S, Nakajima T, Sakamoto T, Watanabe H, Masuda K, Nishimoto Y, Kubo M, Hosoda F, Rokutan H, Matsumoto M, Takamaru H, Yamada M, Matsuda T, Iwasaki M, Yamaji T, Yachida T, Soga T, Kurokawa K, Toyoda A, Ogura Y, Hayashi T, Hatakeyama M, Nakagama H, Saito Y, Fukuda S, Shibata T, Yamada T
Journal
Nature medicine
Year
2019
In most cases of sporadic colorectal cancers, tumorigenesis is a multistep process, involving genomic alterations in parallel with morphologic changes. In addition, accumulating evidence suggests that the human gut microbiome is linked to the development of colorectal cancer. Here we performed fecal metagenomic and metabolomic studies on samples from a large cohort of 616 participants who underwent colonoscopy to assess taxonomic and functional characteristics of gut microbiota and metabolites. Microbiome and metabolome shifts were apparent in cases of multiple polypoid adenomas and intramucosal carcinomas, in addition to more advanced lesions. We found two distinct patterns of microbiome elevations. First, the relative abundance of Fusobacterium nucleatum spp. was significantly (P < 0.005) elevated continuously from intramucosal carcinoma to more advanced stages. Second, Atopobium parvulum and Actinomyces odontolyticus, which co-occurred in intramucosal carcinomas, were significantly (P < 0.005) increased only in multiple polypoid adenomas and/or intramucosal carcinomas. Metabolome analyses showed that branched-chain amino acids and phenylalanine were significantly (P < 0.005) increased in intramucosal carcinomas and bile acids, including deoxycholate, were significantly (P < 0.005) elevated in multiple polypoid adenomas and/or intramucosal carcinomas. We identified metagenomic and metabolomic markers to discriminate cases of intramucosal carcinoma from the healthy controls. Our large-cohort multi-omics data indicate that shifts in the microbiome and metabolome occur from the very early stages of the development of colorectal cancer, which is of possible etiological and diagnostic importance.

Experiment 1


Reviewed Marked as Reviewed by Atrayees on 2023-8-7

Curated date: 2022/06/12

Curator: Jeshudy

Revision editor(s): Jeshudy, WikiWorks, Atrayees

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 control (normal and a few polyps)
Group 1 name Corresponds to the case (exposed) group for case-control studies
stage I/II (SI/II)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
stage I and II CRCs
Group 0 sample size Number of subjects in the control (unexposed) group
251
Group 1 sample size Number of subjects in the case (exposed) group
111
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
None specified

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).
relative abundances
Statistical test
Mann-Whitney (Wilcoxon)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.005
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes


Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-8-7

Curated date: 2022/06/12

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Figure 2B

Description: Species abundances were assessed for significant elevation or depletion (P< 0.005; one-sided Mann–Whitney U test) in each of the four stages, MP (n= 67), S0 (n= 73), SI/II (n= 111) and SIII/IV (n= 74), compared to the healthy controls (n= 251).

Abundance in Group 1: increased abundance in stage I/II (SI/II)

NCBI Quality ControlLinks
Collinsella aerofaciens
Fusobacterium nucleatum
Gemella morbillorum
Lancefieldella parvula
Parvimonas micra
Peptostreptococcus anaerobius
Peptostreptococcus stomatis
Porphyromonas uenonis
Schaalia odontolytica
Solobacterium moorei

Revision editor(s): Jeshudy

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-8-7

Curated date: 2022/06/12

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Figure 2B

Description: Species abundances were assessed for significant elevation or depletion (P< 0.005; one-sided Mann–Whitney U test) in each of the four stages, MP (n= 67), S0 (n= 73), SI/II (n= 111) and SIII/IV (n= 74), compared to the healthy controls (n= 251).

Abundance in Group 1: decreased abundance in stage I/II (SI/II)

NCBI Quality ControlLinks
Bifidobacterium longum subsp. longum
Lachnospira eligens
Lachnospira multipara

Revision editor(s): Jeshudy

Experiment 2


Reviewed Marked as Reviewed by Atrayees on 2023-8-7

Curated date: 2022/06/12

Curator: Jeshudy

Revision editor(s): Jeshudy, WikiWorks, Atrayees

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
stage III/IV (SIII/IV)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
stage III and IV CRCs
Group 1 sample size Number of subjects in the case (exposed) group
74

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-8-7

Curated date: 2022/06/12

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Figure 2B

Description: Phylum distribution of the number of species that are either elevated or depleted in each of the four stages compared to the healthy controls.

Abundance in Group 1: increased abundance in stage III/IV (SIII/IV)

NCBI Quality ControlLinks
Collinsella aerofaciens
Lancefieldella parvula
Schaalia odontolytica
Solobacterium moorei
Porphyromonas uenonis
Fusobacterium nucleatum
Selenomonas sputigena
Gemella morbillorum
Streptococcus anginosus
Fructilactobacillus sanfranciscensis
Parvimonas micra
Dorea longicatena
Peptostreptococcus anaerobius
Peptostreptococcus stomatis
Bilophila wadsworthia
Oleidesulfovibrio vietnamensis

Revision editor(s): Jeshudy

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-8-7

Curated date: 2022/06/12

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Figure 2B

Description: Species abundances were assessed for significant elevation or depletion (P< 0.005; one-sided Mann–Whitney U test) in each of the four stages, MP (n= 67), S0 (n= 73), SI/II (n= 111) and SIII/IV (n= 74), compared to the healthy controls (n= 251).

Abundance in Group 1: decreased abundance in stage III/IV (SIII/IV)

NCBI Quality ControlLinks
Lachnospira eligens
Lachnospira multipara

Revision editor(s): Jeshudy

Experiment 3


Reviewed Marked as Reviewed by Atrayees on 2023-8-7

Curated date: 2022/06/12

Curator: Jeshudy

Revision editor(s): Jeshudy, WikiWorks, Atrayees

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
S0
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
stage 0/pTis CRC (S0)
Group 1 sample size Number of subjects in the case (exposed) group
73

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-8-7

Curated date: 2022/06/12

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Figure 2B

Description: Species abundances were assessed for significant elevation or depletion (P< 0.005; one-sided Mann–Whitney U test) in each of the four stages, MP (n= 67), S0 (n= 73), SI/II (n= 111) and SIII/IV (n= 74), compared to the healthy controls (n= 251).

Abundance in Group 1: increased abundance in S0

NCBI Quality ControlLinks
Lancefieldella parvula
Collinsella aerofaciens
Porphyromonas uenonis
Fusobacterium nucleatum
Actinomyces viscosus
Schaalia odontolytica
Solobacterium moorei
Phascolarctobacterium succinatutens
Gemella morbillorum
Fructilactobacillus sanfranciscensis
Parvimonas micra
Peptostreptococcus stomatis
Desulfovibrio longreachensis

Revision editor(s): Jeshudy

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-8-7

Curated date: 2022/06/12

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Figure 2B

Description: Species abundances were assessed for significant elevation or depletion (P< 0.005; one-sided Mann–Whitney U test) in each of the four stages, MP (n= 67), S0 (n= 73), SI/II (n= 111) and SIII/IV (n= 74), compared to the healthy controls (n= 251).

Abundance in Group 1: decreased abundance in S0

NCBI Quality ControlLinks
Bifidobacterium longum subsp. longum
Lachnospira multipara
Lachnospira eligens

Revision editor(s): Jeshudy

Experiment 4


Reviewed Marked as Reviewed by Atrayees on 2023-8-7

Curated date: 2022/06/12

Curator: Jeshudy

Revision editor(s): Jeshudy, WikiWorks, Atrayees

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
MP
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
multiple polypoid adenomas with low- grade dysplasia (MP, more than three adenomas, mostly more than five adenomas)
Group 1 sample size Number of subjects in the case (exposed) group
67

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-8-7

Curated date: 2022/06/12

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Figure 2B

Description: Species abundances were assessed for significant elevation or depletion (P< 0.005; one-sided Mann–Whitney U test) in each of the four stages, MP (n= 67), S0 (n= 73), SI/II (n= 111) and SIII/IV (n= 74), compared to the healthy controls (n= 251).

Abundance in Group 1: increased abundance in MP

NCBI Quality ControlLinks
Lancefieldella parvula
Fusobacterium nucleatum
Schaalia odontolytica
Phascolarctobacterium succinatutens
Selenomonas sputigena
Oleidesulfovibrio vietnamensis

Revision editor(s): Jeshudy

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-8-7

Curated date: 2022/06/12

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Figure 2B

Description: Species abundances were assessed for significant elevation or depletion (P< 0.005; one-sided Mann–Whitney U test) in each of the four stages, MP (n= 67), S0 (n= 73), SI/II (n= 111) and SIII/IV (n= 74), compared to the healthy controls (n= 251).

Abundance in Group 1: decreased abundance in MP

NCBI Quality ControlLinks
Bifidobacterium longum subsp. longum
Lachnospira multipara
Lachnospira eligens

Revision editor(s): Jeshudy