A signature of Prevotella copri and Faecalibacterium prausnitzii depletion, and a link with bacterial glutamate degradation in the Kenyan colorectal cancer patients

Study information

Needs review

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

36388691

DOI Digital object identifier for electronic documents.

10.21037/jgo-22-116

URI

Authors

Obuya S, Elkholy A, Avuthu N, Behring M, Bajpai P, Agarwal S, Kim HG, El-Nikhely N, Akinyi P, Orwa J, Afaq F, Abdalla M, Michael A, Farouk M, Bateman LB, Fouad M, Saleh M, Guda C, Manne U, Arafat W

Journal

Journal of gastrointestinal oncology

Year

2022

Keywords:

Colorectal cancer (CRC), Faecalibacterium prausnitzii, Kenya, Prevotella copri, microbiome

BACKGROUND: Colorectal cancer (CRC) is the fifth most diagnosed cancer in Sub-Saharan Africa. In Kenya, CRC incidence rates tripled from 1997 to 2017. In the Moi Teaching and Referral Hospital, Moi University, there has been an increase in CRC cases, notably for younger patients. A suggested pathobiology for this increase is gut microbiome dysbiosis. Since, for the Kenyan CRC patient population, microbiome studies are rare, there is a need for a better understanding of how microbiome dysbiosis influences CRC epidemiology in Kenya. In this single-center study, the focus was on profiling the gut microbiome of Kenyan CRC patients and healthy volunteers and evaluating associations between microbiome profiles and the age of CRC patients. METHODS: The gut mucosa-associated microbiome of 18 CRC patients and 18 healthy controls were determined by 16S rRNA sequencing and analyzed for alpha and beta diversity, differential abundance, and microbial metabolic profiling. RESULTS: Alpha diversity metrics showed no significant differences, but beta diversity metrics showed dissimilarities in the microbial communities between CRC patients and healthy controls. The most underrepresented species in the CRC group were Prevotella copri (P. copri) and Faecalibacterium prausnitzii (F. prausnitzii), although Bacteroides fragilis (B. fragilis) and Prevotella nigrescens were overrepresented (linear discriminant analysis, LDA score >2, P<0.05). Also, for CRC patients, significant metagenomic functional alterations were evident in microbial glutamate metabolic pathways (L-glutamate degradation VIII was enriched, and L-glutamate and L-glutamine biosynthesis were diminished) (P<0.05, log2 Fold Change >1). Moreover, the microbiome composition was different for patients under 40 years of age compared to older patients (LDA score >2, P<0.05). CONCLUSIONS: Microbiome and microbial metabolic profiles of CRC patients are different from those of healthy individuals. CRC microbiome dysbiosis, particularly P. copri and F. prausnitzii depletion and glutamate metabolic alterations, are evident in Kenyan CRC patients.

Experiment 1

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Curated date: 2024/10/29

Curator: Ifeanyisam

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Subjects

Location of subjects: Kenya

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: Colon Hindgut,Large bowel,Posterior intestine,Colon,colon

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

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: patients with Colorectal Cancer

Group 0 sample size Number of subjects in the control (unexposed) group: 18

Group 1 sample size Number of subjects in the case (exposed) group: 18

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: 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: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 2.0

Alpha Diversity

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

Chao1 Abundance-based estimator of species richness: unchanged

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

Richness Number of species: unchanged

Signature 1

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Source: Figure 2

Description: Bar graph of LEfSe analysis CRC vs. healthy controls

Abundance in Group 1: increased abundance in CRC Patients

NCBI	Quality Control	Links
Mycoplasma
Mycoplasmatales
Campylobacter ureolyticus
Mycoplasmataceae
Peptostreptococcus anaerobius
Rhodospirillales
Mogibacterium
Anaerococcus
Peptoniphilus
Lactobacillus iners
Mobiluncus
Solobacterium moorei
Helicobacteraceae
Flexispira
Moryella indoligenes
Moryella
1_681_68
Clostridium
Schwartzia
Sporobacterium sp. WAL 1855D
Veillonella dispar
Veillonella parvula
Peptostreptococcus
p_75_a5p_75_a5
Staphylococcaceae
Staphylococcus
Parvimonas
Bacillales
Tissierellaceae
Porphyromonas
Prevotella nigrescens
Fusobacterium
Bacteroides fragilis

Revision editor(s): Ifeanyisam

Signature 2

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Source: Figure 2

Description: Bar graph of LEfSe analysis CRC vs. healthy controls.

Abundance in Group 1: decreased abundance in CRC Patients

NCBI	Quality Control	Links
Actinomycetales
Alcaligenaceae
Alphaproteobacteria
Bacteroides
Bacteroides eggerthii
Burkholderiales
Collinsella
Collinsella aerofaciens
Coriobacteriales
Coriobacteriia
Cyanobacteriota
Dorea formicigenerans
Erysipelotrichaceae
Eubacterium
Faecalibacterium
Faecalibacterium prausnitzii
Haemophilus parainfluenzae
Holdemanella biformis
Parabacteroides
Pasteurellaceae
Pasteurellales
Roseburia
Roseburia faecis
Segatella copri
Sutterella
4COd_24COd_2
YS2YS2
[Ruminococcus] lactaris

Revision editor(s): Ifeanyisam

Experiment 2

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: CRC patients under 40 years of age

Group 1 name Corresponds to the case (exposed) group for case-control studies: CRC Patients over 40 years of age

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients with Colorectal Cancer over 40 years of age