Differences in the gut microbiome by physical activity and BMI among colorectal cancer patients

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Reviewed Marked as Reviewed by Atrayees on 2023-6-1
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Himbert C, Stephens WZ, Gigic B, Hardikar S, Holowatyj AN, Lin T, Ose J, Swanson E, Ashworth A, Warby CA, Peoples AR, Nix D, Jedrzkiewicz J, Bronner M, Pickron B, Scaife C, Cohan JN, Schrotz-King P, Habermann N, Boehm J, Hullar M, Figueiredo JC, Toriola AT, Siegel EM, Li CI, Ulrich AB, Shibata D, Boucher K, Huang LC, Schneider M, Round JL, Ulrich CM
Journal
American journal of cancer research
Year
2022
Keywords:
Colorectal cancer, energy balance, microbiome, obesity, physical activity
Associations of energy balance components, including physical activity and obesity, with colorectal cancer risk and mortality are well established. However, the gut microbiome has not been investigated as underlying mechanism. We investigated associations of physical activity, BMI, and combinations of physical activity/BMI with gut microbiome diversity and differential abundances among colorectal cancer patients. N=179 patients with colorectal cancer (stages I-IV) were included in the study. Pre-surgery stool samples were used to perform 16S rRNA gene sequencing (Illumina). Physical activity (MET hrs/wk) during the year before diagnosis was assessed by questionnaire and participants were classified as being active vs. inactive based on guidelines. BMI at baseline was abstracted from medical records. Patients were classified into four combinations of physical activity levels/BMI. Lower gut microbial diversity was observed among 'inactive' vs. 'active' patients (Shannon: P=0.01, Simpson: P=0.03), 'obese' vs. 'normal weight' patients (Shannon, Simpson, and Observed species: P=0.02, respectively), and 'overweight/obese/inactive' vs. 'normal weight/active' patients (Shannon: P=0.02, Observed species: P=0.04). Results differed by sex and tumor site. Two phyla and 12 genera (Actinobacteria and Fusobacteria, Adlercreutzia, Anaerococcus, Clostridium, Eubacterium, Mogibacteriaceae, Olsenella, Peptinophilus, Pyramidobacter, RFN20, Ruminococcus, Succinivibrio, Succiniclasticum) were differentially abundant across physical activity and BMI groups. This is the first evidence for associations of physical activity with gut microbiome diversity and abundances, directly among colorectal cancer patients. Our results indicate that physical activity may offset gut microbiome dysbiosis due to obesity. Alterations in gut microbiota may contribute mechanistically to the energy balance-colorectal cancer link and impact clinical outcomes.

Experiment 1


Reviewed Marked as Reviewed by Atrayees on 2023-6-1

Curated date: 2023/03/14

Curator: Deacme

Revision editor(s): Deacme, Atrayees, ChiomaBlessing

Subjects

Location of subjects
Germany
United States of America
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
Physical activity Activities, Locomotor,Activities, Motor,Activities, Physical,Activity, Locomotor,Activity, Motor,Activity, Physical,Locomotor Activities,Locomotor Activity,Motor Activities,Motor Activity,Physical Activities,Physical activity,physical activity
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Active patients
Group 1 name Corresponds to the case (exposed) group for case-control studies
Inactive patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients that are not engaged in any regular physical activity or exercise.
Group 0 sample size Number of subjects in the control (unexposed) group
72
Group 1 sample size Number of subjects in the case (exposed) group
107
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
4 weeks

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
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
Wald 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
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
sex, Confounders controlled for: "neoadjuvant treatment" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.neoadjuvant treatment, Confounders controlled for: "stage at diagnosis" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.stage at diagnosis, Confounders controlled for: "study site" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.study site

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-1

Curated date: 2023/03/14

Curator: Deacme

Revision editor(s): Deacme, Atrayees, ChiomaBlessing

Source: Supplementary Table 2

Description: Differential abundance (mean normalized counts) at phylum level inactive group VS active group

Abundance in Group 1: increased abundance in Inactive patients

NCBI Quality ControlLinks
Actinomycetota

Revision editor(s): Deacme, Atrayees, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-1

Curated date: 2023/03/14

Curator: Deacme

Revision editor(s): Deacme, Atrayees, ChiomaBlessing

Source: Table 2

Description: Differential abundance (mean normalized counts) at genus level in inactive group VS active group

Abundance in Group 1: decreased abundance in Inactive patients

NCBI Quality ControlLinks
Succinivibrio
Succiniclasticum

Revision editor(s): Deacme, Atrayees, ChiomaBlessing

Experiment 2


Reviewed Marked as Reviewed by Atrayees on 2023-6-1

Curated date: 2023/03/14

Curator: Deacme

Revision editor(s): Atrayees, Deacme, ChiomaBlessing

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Body mass index BMI,Quetelet's Index,Body mass index,body mass index
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normal weight patients
Group 1 name Corresponds to the case (exposed) group for case-control studies
Overweight patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patient with a BMI greater than or equal to 25 kg/m2 but not greater than 30 kg/m2.
Group 0 sample size Number of subjects in the control (unexposed) group
59
Group 1 sample size Number of subjects in the case (exposed) group
76

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
sex, Confounders controlled for: "study site" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.study site, Confounders controlled for: "neoadjuvant treatment" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.neoadjuvant treatment, Confounders controlled for: "stage at diagnosis" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.stage at diagnosis

Alpha Diversity

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

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-1

Curated date: 2023/03/16

Curator: Deacme

Revision editor(s): Atrayees, Deacme, Aiyshaaaa, ChiomaBlessing

Source: Table 2

Description: Differential abundance (mean normalized counts) at genus level in overweight group VS normal weight group

Abundance in Group 1: decreased abundance in Overweight patients

NCBI Quality ControlLinks
Olsenella
unclassified Mogibacterium
Anaerococcus
Eubacterium
Clostridium
Succiniclasticum
Succinivibrio

Revision editor(s): Atrayees, Deacme, Aiyshaaaa, ChiomaBlessing

Experiment 3


Reviewed Marked as Reviewed by Atrayees on 2023-6-1

Curated date: 2023/03/16

Curator: Deacme

Revision editor(s): Deacme, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Obese patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with a BMI greater than 30 kg/m2
Group 1 sample size Number of subjects in the case (exposed) group
44

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-1

Curated date: 2023/03/16

Curator: Deacme

Revision editor(s): Deacme, Atrayees, ChiomaBlessing

Source: Table 2

Description: Differential abundance (mean normalized counts) at genus level in obese group VS normal weight group

Abundance in Group 1: increased abundance in Obese patients

NCBI Quality ControlLinks
Ruminococcus

Revision editor(s): Deacme, Atrayees, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-1

Curated date: 2023/03/16

Curator: Deacme

Revision editor(s): Deacme, Atrayees, ChiomaBlessing

Source: Table 2

Description: Differential abundance (mean normalized counts) at genus level in obese group VS normal weight group

Abundance in Group 1: decreased abundance in Obese patients

NCBI Quality ControlLinks
Adlercreutzia
Clostridium
Succinivibrio

Revision editor(s): Deacme, Atrayees, ChiomaBlessing

Experiment 4


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-3

Curated date: 2023/03/16

Curator: Deacme

Revision editor(s): Deacme, Atrayees, ChiomaBlessing

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Body mass index , Physical activity BMI,Quetelet's Index,Body mass index,body mass index,Activities, Locomotor,Activities, Motor,Activities, Physical,Activity, Locomotor,Activity, Motor,Activity, Physical,Locomotor Activities,Locomotor Activity,Motor Activities,Motor Activity,Physical Activities,Physical activity,physical activity
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normal weight/active patients
Group 1 name Corresponds to the case (exposed) group for case-control studies
Normal weight/inactive patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patient that has a BMI greater than 18.5 kg/m2 but less than 25 kg/m2 and engaged in little to no physical activity on a regular basis.
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
33

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
sex, Confounders controlled for: "stage at diagnosis" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.stage at diagnosis, Confounders controlled for: "neoadjuvant treatment" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.neoadjuvant treatment, Confounders controlled for: "study site" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.study site

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-4

Curated date: 2024/02/04

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Table 3

Description: Differential abundance (mean normalized counts) at genus level (by individual BMI and physical activity groups) in normal weight/ inactive group compared to normal weight/ active group

Abundance in Group 1: decreased abundance in Normal weight/inactive patients

NCBI Quality ControlLinks
Succiniclasticum
Succinivibrio

Revision editor(s): ChiomaBlessing

Signature 2

Needs review

Curated date: 2024/02/04

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Table 3

Description: Differential abundance (mean normalized counts) at genus level (by individual BMI and physical activity groups) in normal weight/ inactive group compared to normal weight/ active group

Abundance in Group 1: increased abundance in Normal weight/inactive patients

NCBI Quality ControlLinks
Pyramidobacter

Revision editor(s): ChiomaBlessing

Experiment 5


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-3

Curated date: 2023/03/16

Curator: Deacme

Revision editor(s): Deacme, Atrayees, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Overweight/Obese/active patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patient with a BMI greater than or equal to 25 kg/m2 but is also physically active.
Group 1 sample size Number of subjects in the case (exposed) group
46

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-4

Curated date: 2023/03/16

Curator: Deacme

Revision editor(s): Atrayees, Deacme, Aiyshaaaa, ChiomaBlessing

Source: Table 3

Description: Differential abundance (mean normalized counts) at genus level (by individual BMI and physical activity groups) in overweight/ obese active group compared to normal weight active group

Abundance in Group 1: increased abundance in Overweight/Obese/active patients

NCBI Quality ControlLinks
Pyramidobacter

Revision editor(s): Atrayees, Deacme, Aiyshaaaa, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-3

Curated date: 2023/03/16

Curator: Deacme

Revision editor(s): Atrayees, Deacme, Aiyshaaaa, ChiomaBlessing

Source: Table 3 & Supplementary Table 3

Description: Differential abundance (mean normalized counts) at genus and phylum level (by individual BMI and physical activity groups) in overweight/ obese active group compared to normal weight active group

Abundance in Group 1: decreased abundance in Overweight/Obese/active patients

NCBI Quality ControlLinks
Fusobacteriia
Peptoniphilus
Succiniclasticum
Succinivibrio

Revision editor(s): Atrayees, Deacme, Aiyshaaaa, ChiomaBlessing

Experiment 6


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-3

Curated date: 2023/03/16

Curator: Deacme

Revision editor(s): Deacme, Atrayees, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Overweight/Obese/inactive patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patient with a BMI equal to or greater than 25 kg/m2 and is physically inactive.
Group 1 sample size Number of subjects in the case (exposed) group
74

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-3

Curated date: 2023/03/16

Curator: Deacme

Revision editor(s): Atrayees, Deacme, Aiyshaaaa, ChiomaBlessing

Source: Supplementary Table 3

Description: Differential abundances (mean normalized counts) at phylum level (by combined BMI and physical activity groups) in overweight/ obese/ inactive group VS normal weight/ active group

Abundance in Group 1: increased abundance in Overweight/Obese/inactive patients

NCBI Quality ControlLinks
Actinomycetota

Revision editor(s): Atrayees, Deacme, Aiyshaaaa, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-4

Curated date: 2024/02/04

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Table 3

Description: Differential abundances (mean normalized counts) at genus level (by combined BMI and physical activity groups) in overweight/ obese/ inactive group VS normal weight/ active group

Abundance in Group 1: decreased abundance in Overweight/Obese/inactive patients

NCBI Quality ControlLinks
Succinivibrio
RFN20RFN20

Revision editor(s): ChiomaBlessing

Experiment 7


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-3

Curated date: 2023/03/16

Curator: Deacme

Revision editor(s): Deacme, Atrayees, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Overweight/Obese/active patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with BMI greater than or equal to 25 kg/m2 and are not physically active.
Group 0 sample size Number of subjects in the control (unexposed) group
46

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-4

Curated date: 2024/02/04

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Table 3

Description: Differential abundances (mean normalized counts) at genus level by combined BMI and physical activity groups in overweight/ obese inactive group VS overweight/ obese active group

Abundance in Group 1: decreased abundance in Overweight/Obese/inactive patients

NCBI Quality ControlLinks
Succiniclasticum
Succinivibrio

Revision editor(s): ChiomaBlessing