Initial gut microbiota composition is a determining factor in the promotion of colorectal cancer by oral iron supplementation: evidence from a murine model

From BugSigDB
Reviewed Marked as Reviewed by KateRasheed on 2025-6-9
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Cuisiniere T, Hajjar R, Oliero M, Calvé A, Fragoso G, Rendos HV, Gerkins C, Taleb N, Gagnon-Konamna M, Dagbert F, Loungnarath R, Sebajang H, Schwenter F, Wassef R, Ratelle R, De Broux É, Richard C, Santos MM
Journal
Microbiome
Year
2025
Keywords:
Colorectal cancer, Gut microbiota, Iron supplementation
BACKGROUND: Colorectal cancer (CRC) development is influenced by both iron and gut microbiota composition. While iron supplementation is routinely used to manage anemia in CRC patients, it may also impact gut microbiota and promote tumorigenesis. In this study, we investigated the impact of initial gut microbiota composition on iron-promoted tumorigenesis. We performed fecal microbiota transplantation (FMT) in ApcMin/+ mice using samples from healthy controls, CRC patients, and mice, followed by exposure to iron sufficient or iron excess diets. RESULTS: We found that iron supplementation promoted CRC and resulted in distinct gut microbiota changes in ApcMin/+ mice receiving FMT from CRC patients (FMT-CRC), but not from healthy controls or mice. Oral treatment with identified bacterial strains, namely Faecalibaculum rodentium, Holdemanella biformis, Bifidobacterium pseudolongum, and Alistipes inops, protected FMT-CRC mice against iron-promoted tumorigenesis. CONCLUSIONS: Our findings suggest that microbiota-targeted interventions may mitigate tumorigenic effects of iron supplementation in anemic patients with CRC.

Experiment 1


Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/04/25

Curator: Joiejoie

Revision editor(s): Joiejoie, PreciousChijioke

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled. Contact us to have more species added.
Mus musculus
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
Transplant outcome measurement Transplant outcome measurement,transplant outcome measurement
Group 0 name Corresponds to the control (unexposed) group for case-control studies
FMT-HC (Fecal microbiota transplantation from healthy controls) mice fed 50 ppm iron
Group 1 name Corresponds to the case (exposed) group for case-control studies
FMT-HC (Fecal microbiota transplantation from healthy controls) mice fed 500 ppm iron
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group refers to mice that received fecal microbiota transplantation from healthy human controls and were fed an iron excess (500 ppm) diet.
Group 0 sample size Number of subjects in the control (unexposed) group
24
Group 1 sample size Number of subjects in the case (exposed) group
26

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V5-V6
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
T-Test
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
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/04/25

Curator: Joiejoie

Revision editor(s): Joiejoie, PreciousChijioke

Source: Fig. 2B, 2E and S7

Description: Relative abundances of microbial taxa at phylum level.

Abundance in Group 1: increased abundance in FMT-HC (Fecal microbiota transplantation from healthy controls) mice fed 500 ppm iron

NCBI Quality ControlLinks
Bacteroidota
Pseudomonadota
Verrucomicrobiota
Alistipes inops
Romboutsia ilealis

Revision editor(s): Joiejoie, PreciousChijioke

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/04/25

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke, Victoria

Source: Fig. 2B, 2E and S7

Description: Relative abundances of microbial taxa at phylum level.

Abundance in Group 1: decreased abundance in FMT-HC (Fecal microbiota transplantation from healthy controls) mice fed 500 ppm iron

NCBI Quality ControlLinks
Actinomycetota
Bacillota
Bifidobacterium pseudolongum

Revision editor(s): PreciousChijioke, Victoria

Experiment 2


Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/04/25

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke, Joiejoie

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Statistical test
LEfSe
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
3

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/04/25

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke, Victoria

Source: Fig. 2D

Description: Differential bacterial species.

Abundance in Group 1: increased abundance in FMT-HC (Fecal microbiota transplantation from healthy controls) mice fed 500 ppm iron

NCBI Quality ControlLinks
Romboutsia ilealis
Alistipes inops

Revision editor(s): PreciousChijioke, Victoria

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/04/26

Curator: Joiejoie

Revision editor(s): Joiejoie, Victoria

Source: Fig. 2D

Description: Differential bacterial species.

Abundance in Group 1: decreased abundance in FMT-HC (Fecal microbiota transplantation from healthy controls) mice fed 500 ppm iron

NCBI Quality ControlLinks
Bifidobacterium pseudolongum

Revision editor(s): Joiejoie, Victoria

Experiment 3


Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/04/26

Curator: Joiejoie

Revision editor(s): Joiejoie, PreciousChijioke, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
FMT-CRC (Fecal microbiota transplantation from Colorectal cancer patients) mice fed 50 ppm iron
Group 1 name Corresponds to the case (exposed) group for case-control studies
FMT-CRC (Fecal microbiota transplantation from Colorectal cancer patients) mice fed 500 ppm iron
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group refers to mice that received fecal microbiota transplantation from Colorectal cancer patients and were fed an iron excess (500 ppm) diet.
Group 0 sample size Number of subjects in the control (unexposed) group
25
Group 1 sample size Number of subjects in the case (exposed) group
27

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
raw counts
Statistical test
DESeq2

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/04/26

Curator: Joiejoie

Revision editor(s): Joiejoie, PreciousChijioke

Source: Fig. 2C

Description: Relative abundances of microbial taxa at family level.

Abundance in Group 1: increased abundance in FMT-CRC (Fecal microbiota transplantation from Colorectal cancer patients) mice fed 500 ppm iron

NCBI Quality ControlLinks
Enterobacteriaceae

Revision editor(s): Joiejoie, PreciousChijioke

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/04/26

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke, Victoria

Source: Fig. 2C

Description: Relative abundances of microbial taxa at family level.

Abundance in Group 1: decreased abundance in FMT-CRC (Fecal microbiota transplantation from Colorectal cancer patients) mice fed 500 ppm iron

NCBI Quality ControlLinks
Clostridiaceae
Muribaculaceae

Revision editor(s): PreciousChijioke, Victoria

Experiment 4


Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/04/26

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke, Victoria

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
FMT-CRC (Fecal microbiota transplantation from Colorectal cancer patients) mice fed 500 ppm iron

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
T-Test
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/04/26

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke, Victoria

Source: Fig. 2B, 2E and S7

Description: Relative abundances of microbial taxa at phylum level.

Abundance in Group 1: increased abundance in FMT-CRC (Fecal microbiota transplantation from Colorectal cancer patients) mice fed 500 ppm iron

NCBI Quality ControlLinks
Bacteroidota
Pseudomonadota
Romboutsia ilealis
Verrucomicrobiota

Revision editor(s): PreciousChijioke, Victoria

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/04/28

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke

Source: Fig. 2B, 2E and S7

Description: Relative abundances of microbial taxa at phylum level.

Abundance in Group 1: decreased abundance in FMT-CRC (Fecal microbiota transplantation from Colorectal cancer patients) mice fed 500 ppm iron

NCBI Quality ControlLinks
Actinomycetota
Bacillota
Faecalibaculum rodentium
Bifidobacterium pseudolongum

Revision editor(s): PreciousChijioke

Experiment 5


Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/05/09

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
FMT-CRC (Fecal microbiota transplantation from Colorectal cancer patients) mice fed 500 ppm iron

Lab analysis

Statistical Analysis

Statistical test
LEfSe
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
3

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/05/09

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke

Source: Fig. 2D

Description: Differential bacterial species.

Abundance in Group 1: increased abundance in FMT-CRC (Fecal microbiota transplantation from Colorectal cancer patients) mice fed 500 ppm iron

NCBI Quality ControlLinks
Romboutsia ilealis

Revision editor(s): PreciousChijioke

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/05/09

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke

Source: Fig. 2D

Description: Differential bacterial species.

Abundance in Group 1: decreased abundance in FMT-CRC (Fecal microbiota transplantation from Colorectal cancer patients) mice fed 500 ppm iron

NCBI Quality ControlLinks
Bifidobacterium pseudolongum
Faecalibaculum rodentium

Revision editor(s): PreciousChijioke

Experiment 6


Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/05/09

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
FMT-HC (Fecal microbiota transplantation from healthy controls) mice fed 50 ppm iron
Group 1 name Corresponds to the case (exposed) group for case-control studies
FMT-HC (Fecal microbiota transplantation from healthy controls) mice fed 500 ppm iron
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group refers to mice that received fecal microbiota transplantation from healthy human controls and were fed an iron excess (500 ppm) diet.
Group 0 sample size Number of subjects in the control (unexposed) group
24
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
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/05/09

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke

Source: Fig. 2C

Description: Relative abundances of microbial taxa at family level.

Abundance in Group 1: increased abundance in FMT-HC (Fecal microbiota transplantation from healthy controls) mice fed 500 ppm iron

NCBI Quality ControlLinks
Enterobacteriaceae

Revision editor(s): PreciousChijioke

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/05/09

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke, Victoria

Source: Fig. 2C

Description: Relative abundances of microbial taxa at family level.

Abundance in Group 1: decreased abundance in FMT-HC (Fecal microbiota transplantation from healthy controls) mice fed 500 ppm iron

NCBI Quality ControlLinks
Peptostreptococcaceae
Streptococcaceae

Revision editor(s): PreciousChijioke, Victoria

Experiment 7


Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/05/13

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Diet measurement Diet measurement,diet measurement
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Mice fed with Saline 50ppm
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mice fed with Saline 500ppm
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group refers to mice that received fecal microbiota transplantation from Colorectal cancer patients and were fed a saline (500 ppm) diet.
Group 0 sample size Number of subjects in the control (unexposed) group
Not specified
Group 1 sample size Number of subjects in the case (exposed) group
Not specified

Lab analysis

Statistical Analysis

Statistical test
ANOVA
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified


Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/05/13

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke, Victoria

Source: Fig. 4B

Description: Fecal levels of F. rodentium (Fr) and H. biformis (Hb) quantified by real-time PCR in mice at endpoint.

Abundance in Group 1: decreased abundance in Mice fed with Saline 500ppm

NCBI Quality ControlLinks
Faecalibaculum rodentium

Revision editor(s): PreciousChijioke, Victoria

Experiment 8


Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/05/13

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke, Victoria

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group refers to mice that received fecal microbiota transplantation from Colorectal cancer patients and were fed with a Saline (500 ppm) diet.

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/05/13

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke, Victoria

Source: Fig. 5B

Description: Fecal levels of A. inops (Ai) and B. pseudolongum (Bp) quantified by real-time PCR in mice at endpoint.

Abundance in Group 1: increased abundance in Mice fed with Saline 500ppm

NCBI Quality ControlLinks
Alistipes inops

Revision editor(s): PreciousChijioke, Victoria

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/06/05

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5B

Description: Fecal levels of A. inops (Ai) and B. pseudolongum (Bp) quantified by real-time PCR in mice at endpoint.

Abundance in Group 1: decreased abundance in Mice fed with Saline 500ppm

NCBI Quality ControlLinks
Bifidobacterium pseudolongum

Revision editor(s): Victoria

Experiment 9


Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/06/05

Curator: Victoria

Revision editor(s): Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Mice fed with Saline 500ppm
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mice fed with F. rodentium strain ALO17 (Fr) 500ppm by weekly gavage
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group refers to mice that received fecal microbiota transplantation from Colorectal cancer patients and were fed with F. rodentium strain ALO17 (Fr) 500ppm by weekly gavage.

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/06/05

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 4B

Description: Fecal levels of F. rodentium (Fr) quantified by real-time PCR in mice at endpoint.

Abundance in Group 1: increased abundance in Mice fed with F. rodentium strain ALO17 (Fr) 500ppm by weekly gavage

NCBI Quality ControlLinks
Faecalibaculum rodentium

Revision editor(s): Victoria

Experiment 10


Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/06/05

Curator: Victoria

Revision editor(s): Victoria

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Mice fed with H. biformis strain VPI C17 - 5 (Hb) 500ppm by weekly gavage
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group refers to mice that received fecal microbiota transplantation from Colorectal cancer patients and were fed with H. biformis strain VPI C17 - 5 (Hb) 500ppm by weekly gavage.

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/06/05

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 4B

Description: Fecal levels of H. biformis (Hb) quantified by real-time PCR in mice at endpoint.

Abundance in Group 1: increased abundance in Mice fed with H. biformis strain VPI C17 - 5 (Hb) 500ppm by weekly gavage

NCBI Quality ControlLinks
Holdemanella biformis

Revision editor(s): Victoria

Experiment 11


Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/06/05

Curator: Victoria

Revision editor(s): Victoria

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Mice fed with Alistipes inops strain 627 (Ai) 500ppm by weekly gavage
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group refers to mice that received fecal microbiota transplantation from Colorectal cancer patients and were fed with Alistipes inops strain 627 (Ai) 500ppm by weekly gavage.

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/06/05

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5B

Description: Fecal levels of A. inops (Ai) quantified by real-time PCR in mice at endpoint.

Abundance in Group 1: increased abundance in Mice fed with Alistipes inops strain 627 (Ai) 500ppm by weekly gavage

NCBI Quality ControlLinks
Alistipes inops

Revision editor(s): Victoria

Experiment 12


Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/06/05

Curator: Victoria

Revision editor(s): Victoria

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Mice fed with Bifidobacterium pseudolongum strain 28 T (Bp) 500ppm by weekly gavage
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group refers to mice that received fecal microbiota transplantation from Colorectal cancer patients and were fed with Bifidobacterium pseudolongum strain 28 T (Bp) 500ppm by weekly gavage.

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-9

Curated date: 2025/06/05

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5B

Description: Fecal levels of B. pseudolongum (Bp) quantified by real-time PCR in mice at endpoint.

Abundance in Group 1: increased abundance in Mice fed with Bifidobacterium pseudolongum strain 28 T (Bp) 500ppm by weekly gavage

NCBI Quality ControlLinks
Bifidobacterium pseudolongum

Revision editor(s): Victoria