The potential of fecal microbiota and amino acids to detect and monitor patients with adenoma

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Reviewed Marked as Reviewed by Atrayees on 2023-7-17
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Bosch S, Acharjee A, Quraishi MN, Rojas P, Bakkali A, Jansen EE, Brizzio Brentar M, Kuijvenhoven J, Stokkers P, Struys E, Beggs AD, Gkoutos GV, de Meij TG, de Boer NK
Journal
Gut microbes
Year
2022
Keywords:
Omics, adenoma, biomarker, colorectal cancer, surveillance
The risk of recurrent dysplastic colonic lesions is increased following polypectomy. Yield of endoscopic surveillance after adenoma removal is low, while interval colorectal cancers occur. To longitudinally assess the dynamics of fecal microbiota and amino acids in the presence of adenomatous lesions and after their endoscopic removal. In this longitudinal case-control study, patients collected fecal samples prior to bowel preparation before scheduled colonoscopy and 3 months after this intervention. Based on colonoscopy outcomes, patients with advanced adenomas and nonadvanced adenomas (0.5-1.0 cm) who underwent polypectomy during endoscopy (n = 19) were strictly matched on age, body-mass index, and smoking habits to controls without endoscopic abnormalities (n = 19). Microbial taxa were measured by 16S RNA sequencing, and amino acids (AA) were measured by high-performance liquid chromatography (HPLC). Adenoma patients were discriminated from controls based on AA and microbial composition. Levels of proline (p = .001), ornithine (p = .02) and serine (p = .02) were increased in adenoma patients compared to controls but decreased to resemble those of controls after adenoma removal. These AAs were combined as a potential adenoma-specific panel (AUC 0.79(0.64-0.94)). For bacterial taxa, differences between patients with adenomas and controls were found (Bifidobacterium spp.↓, Anaerostipes spp.↓, Butyricimonas spp.↑, Faecalitalea spp.↑ and Catenibacterium spp.↑), but no alterations in relative abundance were observed after polypectomy. Furthermore, Faecalitalea spp. and Butyricimonas spp. were significantly correlated with adenoma-specific amino acids. We selected an amino acid panel specifically increased in the presence of adenomas and a microbial signature present in adenoma patients, irrespective of polypectomy. Upon validation, these panels may improve the effectiveness of the surveillance program by detection of high-risk individuals and determination of surveillance endoscopy timing, leading to less unnecessary endoscopies and less interval cancer.

Experiment 1


Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2022/07/31

Curator: Jeshudy

Revision editor(s): Jeshudy, WikiWorks, Atrayees

Subjects

Location of subjects
Netherlands
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Intestine Bowel,Intestinal tract,Intestine
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
colorectal adenoma adenoma of large bowel,adenoma of large intestine,adenoma of the large bowel,adenoma of the large intestine,colorectal adenoma,colorectum adenoma,large bowel adenoma,large intestine adenoma
Group 0 name Corresponds to the control (unexposed) group for case-control studies
non-adenoma group
Group 1 name Corresponds to the case (exposed) group for case-control studies
adenoma group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with a successful polypectomy. A total of 9 patients had advanced adenomas and 10 patients had non-advanced adenoma (NA), with a median size of the largest adenoma being 0.7 cm [IQR 0.5–0.8].

PRIOR to polypectomy.

Group 0 sample size Number of subjects in the control (unexposed) group
32
Group 1 sample size Number of subjects in the case (exposed) group
32
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 months prior to study inclusion and 3 months prior to second sample

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)
2
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2
Matched on Factors on which subjects have been matched on in a case-control study
age, body mass index, smoking behavior

Alpha Diversity

Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2022/07/31

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Figure 2

Description: Distribution of selected taxa for adenomas versus controls at baseline

Abundance in Group 1: increased abundance in adenoma group

NCBI Quality ControlLinks
Butyricimonas
Catenibacterium
Sutterella

Revision editor(s): Jeshudy

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2022/07/31

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Figure 2

Description: Distribution of selected taxa for adenomas versus controls at baseline

Abundance in Group 1: decreased abundance in adenoma group

NCBI Quality ControlLinks
Anaerostipes
Bifidobacterium
Faecalitalea
Candidatus Gastranaerophilales

Revision editor(s): Jeshudy

Experiment 2


Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2022/07/31

Curator: Jeshudy

Revision editor(s): Jeshudy, WikiWorks, Atrayees

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with a successful polypectomy. A total of 9 patients had advanced adenomas and 10 patients had non-advanced adenoma (NA), with a median size of the largest adenoma being 0.7 cm [IQR 0.5–0.8].
Group 0 sample size Number of subjects in the control (unexposed) group
19
Group 1 sample size Number of subjects in the case (exposed) group
19

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
Not specified
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
Matched on Factors on which subjects have been matched on in a case-control study
smoking status, age, body mass index

Alpha Diversity

Richness Number of species
unchanged

Experiment 3


Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2022/07/31

Curator: Jeshudy

Revision editor(s): Jeshudy, WikiWorks

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with a successful polypectomy. A total of 9 patients had advanced adenomas and 10 patients had non-advanced adenoma (NA), with a median size of the largest adenoma being 0.7 cm [IQR 0.5–0.8].

POST polypectomy.

Group 0 sample size Number of subjects in the control (unexposed) group
32
Group 1 sample size Number of subjects in the case (exposed) group
32

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
Not specified

Alpha Diversity

Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2022/07/31

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Figure 2

Description: Distribution of selected taxa for adenomas versus controls at follow-up.

Abundance in Group 1: decreased abundance in adenoma group

NCBI Quality ControlLinks
Candidatus Gastranaerophilales
Bifidobacterium

Revision editor(s): Jeshudy

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2022/07/31

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Figure 2

Description: Distribution of selected taxa for adenomas versus controls at follow-up.

Abundance in Group 1: increased abundance in adenoma group

NCBI Quality ControlLinks
Sutterella

Revision editor(s): Jeshudy

Experiment 4


Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2022/07/31

Curator: Jeshudy

Revision editor(s): Jeshudy, WikiWorks

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
adenoma group pre-polypectomy
Group 1 name Corresponds to the case (exposed) group for case-control studies
adenoma group post-polypectomy
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with a successful polypectomy. A total of 9 patients had advanced adenomas and 10 patients had non-advanced adenoma (NA), with a median size of the largest adenoma being 0.7 cm [IQR 0.5–0.8].

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
Matched on: "subject" 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.subject


Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2022/07/31

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Figure 3

Description: Distribution of selected taxa for baseline versus follow-up.

Abundance in Group 1: increased abundance in adenoma group post-polypectomy

NCBI Quality ControlLinks
Anaerobutyricum hallii
unclassified Candidatus Izimaplasma
unclassified Enterobacteriaceae
unclassified Puniceicoccaceae
unclassified Clostridium

Revision editor(s): Jeshudy

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2022/07/31

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Figure 2

Description: Distribution of selected taxa for adenomas at baseline and follow-up.

Abundance in Group 1: increased abundance in adenoma group post-polypectomy

NCBI Quality ControlLinks
Candidatus Gastranaerophilales

Revision editor(s): Jeshudy

Experiment 5


Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2022/07/31

Curator: Jeshudy

Revision editor(s): Jeshudy, WikiWorks

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
control group pre-endoscopy
Group 1 name Corresponds to the case (exposed) group for case-control studies
control group post-endoscopy
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with a successful endoscopy.

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2022/07/31

Curator: Jeshudy

Revision editor(s): Jeshudy, Atrayees

Source: Figure 2, 3

Description: Distribution of selected taxa for baseline versus follow-up

Abundance in Group 1: increased abundance in control group post-endoscopy

NCBI Quality ControlLinks
Anaerobutyricum hallii
Desulfovibrio
Dialister
Streptococcus
Victivallis
unclassified Candidatus Izimaplasma
unclassified Puniceicoccaceae
unclassified Clostridium
Candidatus Gastranaerophilales

Revision editor(s): Jeshudy, Atrayees

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2022/07/31

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Figure 3

Description: Distribution of selected taxa for baseline versus follow-up

Abundance in Group 1: decreased abundance in control group post-endoscopy

NCBI Quality ControlLinks
Lachnospiraceae

Revision editor(s): Jeshudy