Alteration of fecal tryptophan metabolism correlates with shifted microbiota and may be involved in pathogenesis of colorectal cancer
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Sun XZ, Zhao DY, Zhou YC, Wang QQ, Qin G, Yao SK
Journal
World journal of gastroenterology
Year
2020
Keywords:
Colorectal adenoma, Colorectal cancer, Indoles, Kynurenine, Microbiota, Tryptophan metabolism
BACKGROUND: Gut tryptophan (Trp) metabolites are produced by microbiota and/or host metabolism. Some of them have been proven to promote or inhibit colorectal cancer (CRC) in vitro and animal models. We hypothesized that there is an alteration of gut Trp metabolism mediated by microbiota and that it might be involved in the pathogenesis of cancer in patients with CRC. AIM: To investigate the features of Trp metabolism in CRC and the correlation between fecal Trp metabolites and gut microbiota. METHODS: Seventy-nine patients with colorectal neoplastic lesions (33 with colon adenoma and 46 with sporadic CRC) and 38 healthy controls (HCs) meeting the inclusion and exclusion criteria were included in the study. Their demographic and clinical features were collected. Fecal Trp, kynurenine (KYN), and indoles (metabolites of Trp metabolized by gut microbiota) were examined by ultraperformance liquid chromatography coupled to tandem mass spectrometry. Gut barrier marker and indoleamine 2,3-dioxygenase 1 (IDO1) mRNA were analyzed by quantitative real-time polymerase chain reaction. Zonula occludens-1 (ZO-1) protein expression was analyzed by immunohistochemistry. The gut microbiota was detected by 16S ribosomal RNA gene sequencing. Correlations between fecal metabolites and other parameters were examined in all patients. RESULTS: The absolute concentration of KYN [1.51 (0.70, 3.46) nmol/g vs 0.81 (0.64, 1.57) nmol/g, P = 0.036] and the ratio of KYN to Trp [7.39 (4.12, 11.72) × 10-3 vs 5.23 (1.86, 7.99) × 10-3, P = 0.032] were increased in the feces of patients with CRC compared to HCs, while the indoles to Trp ratio was decreased [1.34 (0.70, 2.63) vs 2.46 (1.25, 4.10), P = 0.029]. The relative ZO-1 mRNA levels in patients with CRC (0.27 ± 0.24) were significantly lower than those in HCs (1.00 ± 0.31) (P < 0.001), and the relative IDO1 mRNA levels in patients with CRC [1.65 (0.47-2.46)] were increased (P = 0.035). IDO1 mRNA levels were positively associated with the KYN/Trp ratio (r = 0.327, P = 0.003). ZO-1 mRNA and protein levels were positively correlated with the indoles/Trp ratio (P = 0.035 and P = 0.009, respectively). In addition, the genera Asaccharobacter (Actinobacteria) and Parabacteroides (Bacteroidetes), and members of the phylum Firmicutes (Clostridium XlVb, Fusicatenibacter, Anaerofilum, and Anaerostipes) decreased in CRC and exhibited a positive correlation with indoles in all subjects. CONCLUSION: Alteration of fecal Trp metabolism mediated by microbiota is associated with intestinal barrier function and tissue Trp metabolism, and may be involved in the pathogenesis of CRC.
Experiment 1
Reviewed Marked as Reviewed by Chloe on 2022/03/11
Curated date: 2022/01/26
Curator: Itslanapark
Revision editor(s): WikiWorks, Chloe, Itslanapark, Peace Sandy
Subjects
- Location of subjects
- China
- 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 Controls (HC)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- CRC
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with colorectal neoplastic lesions where tumors were removed and pathologically diagnosed with adenomatous polyp or colorectal adenocarcinoma; ages of participants ranged from 18-80.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 38
- Group 1 sample size Number of subjects in the case (exposed) group
- 79
- 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
- LEfSe
- 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)?
- No
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2.0
- Matched on Factors on which subjects have been matched on in a case-control study
- age, body mass index, sex
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Chloe on 2022/03/11
Curated date: 2022/01/31
Curator: Itslanapark
Revision editor(s): Chloe, Itslanapark, Merit, Aiyshaaaa
Source: Figure 4C
Description: Linear discriminant analysis effect size analysis of fecal bacterial of colorectal cancer patients and HCs was used to represent which taxa were increased in CRC patients and which were enriched in healthy controls. Taxa enriched in HCs are indicated with a negative LDA score and taxa enriched in the CRC group are indicated with a positive LDA score.
Abundance in Group 1: increased abundance in CRC
Revision editor(s): Chloe, Itslanapark, Merit, Aiyshaaaa
Signature 2
Reviewed Marked as Reviewed by Chloe on 2022/03/11
Source: Figure 4c
Description: Linear discriminant analysis effect size analysis of fecal bacterial of colorectal cancer patients and HCs was used to represent which taxa were increased in CRC patients and which were enriched in healthy controls. Taxa enriched in HCs are indicated with a negative LDA score and taxa enriched in the CRC group are indicated with a positive LDA score.
Abundance in Group 1: decreased abundance in CRC
Revision editor(s): Fatima, Chloe, Itslanapark, Merit
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