Skip to main content
Top
Published in: Gut Pathogens 1/2022

Open Access 01-12-2022 | Respiratory Microbiota | Research

Metagenomic analysis of the interaction between the gut microbiota and colorectal cancer: a paired-sample study based on the GMrepo database

Authors: Han Chen, Jianhua Jiao, Min Wei, Xingzhou Jiang, Ruoyun Yang, Xin Yu, Guoxin Zhang, Xiaoying Zhou

Published in: Gut Pathogens | Issue 1/2022

Login to get access

Abstract

Background

Previous evidence has shown that the gut microbiota plays a role in the development and progression of colorectal cancer (CRC). This study aimed to provide quantitative analysis and visualization of the interaction between the gut microbiota and CRC in order to establish a more precise microbiota panel for CRC diagnosis.

Method

A paired-sample study was designed by retrieving original metagenomic data from the GMrepo database. The differences in the distribution of the gut microbiota between CRCs and controls were analysed at the species level. A co-occurrence network was established, and the microbial interactions with environmental factors were assessed. Random forest models were used to determine significant biomarkers for differentiating CRC and control samples.

Results

A total of 709 metagenomic samples from 6 projects were identified. After matching, 86 CRC patients and 86 matched healthy controls from six countries were enrolled. A total of 484 microbial species and 166 related genera were analysed. In addition to previously recognized associations between Fusobacterium nucleatum and species belonging to the genera Peptostreptococcus, Porphyromonas, and Prevotella and CRC, we found new associations with the novel species of Parvimonas micra and Collinsella tanakaei. In CRC patients, Bacteroides uniformis and Collinsella tanakaei were positively correlated with age, whereas Dorea longicatena, Adlercreutzia equolifaciens, and Eubacterium hallii had positive associations with body mass index (BMI). Finally, a random forest model was established by integrating different numbers of species with the highest model-building importance and lowest inner subcategory bias. The median value of the area under the receiver operating characteristic curve (AUC) was 0.812 in the training cohort and 0.790 in the validation set.

Conclusions

Our study provides a novel bioinformatics approach for investigating the interaction between the gut microbiota and CRC using an online free database. The identification of key species and their associated genes should be further emphasized to determine the relative causality of microbial organisms in the development of CRC.
Appendix
Available only for authorised users
Literature
1.
go back to reference Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer JClin. 2022;72(1):7–33.CrossRef Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer JClin. 2022;72(1):7–33.CrossRef
2.
go back to reference Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet. 2019;394(10207):1467–80.CrossRef Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet. 2019;394(10207):1467–80.CrossRef
3.
go back to reference Yu J, Feng Q, Wong SH, Zhang D, Liang QY, Qin Y, et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut. 2017;66(1):70–8.CrossRef Yu J, Feng Q, Wong SH, Zhang D, Liang QY, Qin Y, et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut. 2017;66(1):70–8.CrossRef
4.
go back to reference Wong SH, Yu J. Gut microbiota in colorectal cancer: mechanisms of action and clinical applications. Nat Rev Gastroenterol Hepatol. 2019;16(11):690–704.CrossRef Wong SH, Yu J. Gut microbiota in colorectal cancer: mechanisms of action and clinical applications. Nat Rev Gastroenterol Hepatol. 2019;16(11):690–704.CrossRef
5.
go back to reference Kim J, Lee HK. Potential role of the gut microbiome in colorectal cancer progression. Front Immunol. 2022;12: 807648.CrossRef Kim J, Lee HK. Potential role of the gut microbiome in colorectal cancer progression. Front Immunol. 2022;12: 807648.CrossRef
6.
go back to reference Song M, Chan AT. Environmental factors, gut microbiota, and colorectal cancer prevention. Clin Gastroenterol Hepatol. 2019;17(2):275–89.CrossRef Song M, Chan AT. Environmental factors, gut microbiota, and colorectal cancer prevention. Clin Gastroenterol Hepatol. 2019;17(2):275–89.CrossRef
7.
go back to reference Feng Q, Liang S, Jia H, Stadlmayr A, Tang L, Lan Z, et al. Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat Commun. 2015;6:6528.CrossRef Feng Q, Liang S, Jia H, Stadlmayr A, Tang L, Lan Z, et al. Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat Commun. 2015;6:6528.CrossRef
8.
go back to reference Liu W, Zhang X, Xu H, Li S, Lau HC, Chen Q, et al. Microbial community heterogeneity within colorectal neoplasia and its correlation with colorectal carcinogenesis. Gastroenterology. 2021;160(7):2395–408.CrossRef Liu W, Zhang X, Xu H, Li S, Lau HC, Chen Q, et al. Microbial community heterogeneity within colorectal neoplasia and its correlation with colorectal carcinogenesis. Gastroenterology. 2021;160(7):2395–408.CrossRef
9.
go back to reference Boleij A, Hechenbleikner EM, Goodwin AC, Badani R, Stein EM, Lazarev MG, et al. The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients. Clin Infect Dis. 2015;60(2):208–15.CrossRef Boleij A, Hechenbleikner EM, Goodwin AC, Badani R, Stein EM, Lazarev MG, et al. The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients. Clin Infect Dis. 2015;60(2):208–15.CrossRef
10.
go back to reference Eklöf V, Löfgren-Burström A, Zingmark C, Edin S, Larsson P, Karling P, et al. Cancer-associated fecal microbial markers in colorectal cancer detection. Int J Cancer. 2017;141(12):2528–36.CrossRef Eklöf V, Löfgren-Burström A, Zingmark C, Edin S, Larsson P, Karling P, et al. Cancer-associated fecal microbial markers in colorectal cancer detection. Int J Cancer. 2017;141(12):2528–36.CrossRef
11.
go back to reference Tsoi H, Chu ESH, Zhang X, Sheng J, Nakatsu G, Ng SC, et al. Peptostreptococcus anaerobius induces intracellular cholesterol biosynthesis in colon cells to induce proliferation and causes dysplasia in mice. Gastroenterology. 2017;152(6):1419-1433.e5.CrossRef Tsoi H, Chu ESH, Zhang X, Sheng J, Nakatsu G, Ng SC, et al. Peptostreptococcus anaerobius induces intracellular cholesterol biosynthesis in colon cells to induce proliferation and causes dysplasia in mice. Gastroenterology. 2017;152(6):1419-1433.e5.CrossRef
12.
go back to reference Wu S, Sun C, Li Y, Wang T, Jia L, Lai S, et al. GMrepo: a database of curated and consistently annotated human gut metagenomes. Nucleic Acids Res. 2020;48(D1):D545–53.CrossRef Wu S, Sun C, Li Y, Wang T, Jia L, Lai S, et al. GMrepo: a database of curated and consistently annotated human gut metagenomes. Nucleic Acids Res. 2020;48(D1):D545–53.CrossRef
13.
go back to reference Hultcrantz R. Aspects of colorectal cancer screening, methods, age and gender. J Intern Med. 2021;289(4):493–507.CrossRef Hultcrantz R. Aspects of colorectal cancer screening, methods, age and gender. J Intern Med. 2021;289(4):493–507.CrossRef
14.
go back to reference Li J, Ma X, Chakravarti D, Shalapour S, DePinho RA. Genetic and biological hallmarks of colorectal cancer. Genes Dev. 2021;35(11–12):787–820.CrossRef Li J, Ma X, Chakravarti D, Shalapour S, DePinho RA. Genetic and biological hallmarks of colorectal cancer. Genes Dev. 2021;35(11–12):787–820.CrossRef
15.
go back to reference Kyrgiou M, Kalliala I, Markozannes G, Gunter MJ, Paraskevaidis E, Gabra H, et al. Adiposity and cancer at major anatomical sites: umbrella review of the literature. BMJ. 2017;356: j477.CrossRef Kyrgiou M, Kalliala I, Markozannes G, Gunter MJ, Paraskevaidis E, Gabra H, et al. Adiposity and cancer at major anatomical sites: umbrella review of the literature. BMJ. 2017;356: j477.CrossRef
16.
go back to reference Subramanian S, Huq S, Yatsunenko T, Haque R, Mahfuz M, Alam MA, et al. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature. 2014;510(7505):417–21.CrossRef Subramanian S, Huq S, Yatsunenko T, Haque R, Mahfuz M, Alam MA, et al. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature. 2014;510(7505):417–21.CrossRef
17.
go back to reference Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12:R60.CrossRef Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12:R60.CrossRef
18.
go back to reference Douglas GM, Maffei VJ, Zaneveld JR, Yurgel SN, Brown JR, Taylor CM, et al. PICRUSt2 for prediction of metagenome functions. Nat Biotechnol. 2020;38(6):685–8.CrossRef Douglas GM, Maffei VJ, Zaneveld JR, Yurgel SN, Brown JR, Taylor CM, et al. PICRUSt2 for prediction of metagenome functions. Nat Biotechnol. 2020;38(6):685–8.CrossRef
19.
go back to reference Liaw AWM. Classification and regression by randomForest. R news. 2002;2:18–22. Liaw AWM. Classification and regression by randomForest. R news. 2002;2:18–22.
20.
go back to reference Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez JC, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011;12:77.CrossRef Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez JC, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011;12:77.CrossRef
21.
go back to reference Wirbel J, Pyl PT, Kartal E, Zych K, Kashani A, Milanese A, et al. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat Med. 2019;25(4):679–89.CrossRef Wirbel J, Pyl PT, Kartal E, Zych K, Kashani A, Milanese A, et al. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat Med. 2019;25(4):679–89.CrossRef
22.
go back to reference Ahn J, Sinha R, Pei Z, Dominianni C, Wu J, Shi J, et al. Human gut microbiome and risk for colorectal cancer. J Natl Cancer Inst. 2013;105(24):1907–11.CrossRef Ahn J, Sinha R, Pei Z, Dominianni C, Wu J, Shi J, et al. Human gut microbiome and risk for colorectal cancer. J Natl Cancer Inst. 2013;105(24):1907–11.CrossRef
23.
go back to reference Dai Z, Coker OO, Nakatsu G, Wu WKK, Zhao L, Chen Z, et al. Multi-cohort analysis of colorectal cancer metagenome identified altered bacteria across populations and universal bacterial markers. Microbiome. 2018;6(1):70.CrossRef Dai Z, Coker OO, Nakatsu G, Wu WKK, Zhao L, Chen Z, et al. Multi-cohort analysis of colorectal cancer metagenome identified altered bacteria across populations and universal bacterial markers. Microbiome. 2018;6(1):70.CrossRef
24.
go back to reference Osman MA, Neoh HM, Ab Mutalib NS, Chin SF, Mazlan L, Raja Ali RA, et al. Parvimonas micra, Peptostreptococcus stomatis, Fusobacterium nucleatum and Akkermansia muciniphila as a four-bacteria biomarker panel of colorectal cancer. Sci Rep. 2021;11(1):2925.CrossRef Osman MA, Neoh HM, Ab Mutalib NS, Chin SF, Mazlan L, Raja Ali RA, et al. Parvimonas micra, Peptostreptococcus stomatis, Fusobacterium nucleatum and Akkermansia muciniphila as a four-bacteria biomarker panel of colorectal cancer. Sci Rep. 2021;11(1):2925.CrossRef
25.
go back to reference Dingemanse C, Belzer C, van Hijum SA, Günthel M, Salvatori D, den Dunnen JT, et al. Akkermansia muciniphila and Helicobacter typhlonius modulate intestinal tumor development in mice. Carcinogenesis. 2015;36(11):1388–96.CrossRef Dingemanse C, Belzer C, van Hijum SA, Günthel M, Salvatori D, den Dunnen JT, et al. Akkermansia muciniphila and Helicobacter typhlonius modulate intestinal tumor development in mice. Carcinogenesis. 2015;36(11):1388–96.CrossRef
26.
go back to reference Wang F, Cai K, Xiao Q, He L, Xie L, Liu Z. Akkermansia muciniphila administration exacerbated the development of colitis-associated colorectal cancer in mice. J Cancer. 2022;13(1):124–33.CrossRef Wang F, Cai K, Xiao Q, He L, Xie L, Liu Z. Akkermansia muciniphila administration exacerbated the development of colitis-associated colorectal cancer in mice. J Cancer. 2022;13(1):124–33.CrossRef
27.
go back to reference Fan L, Xu C, Ge Q, Lin Y, Wong CC, Qi Y, et al. A Muciniphila suppresses colorectal tumorigenesis by inducing TLR2/NLRP3-mediated M1-like TAMs. Cancer Immunol Res. 2021;9(10):1111–24.CrossRef Fan L, Xu C, Ge Q, Lin Y, Wong CC, Qi Y, et al. A Muciniphila suppresses colorectal tumorigenesis by inducing TLR2/NLRP3-mediated M1-like TAMs. Cancer Immunol Res. 2021;9(10):1111–24.CrossRef
28.
go back to reference Doden HL, Wolf PG, Gaskins HR, Anantharaman K, Alves JMP, Ridlon JM. Completion of the gut microbial epi-bile acid pathway. Gut Microbes. 2021;13(1):1–20.CrossRef Doden HL, Wolf PG, Gaskins HR, Anantharaman K, Alves JMP, Ridlon JM. Completion of the gut microbial epi-bile acid pathway. Gut Microbes. 2021;13(1):1–20.CrossRef
29.
go back to reference Graboń W, Otto-Ślusarczyk D, Chrzanowska A, Mielczarek-Puta M, Joniec-Maciejak I, Słabik K, et al. Lactate formation in primary and metastatic colon cancer cells at hypoxia and normoxia. Cell Biochem Funct. 2016;34(7):483–90.CrossRef Graboń W, Otto-Ślusarczyk D, Chrzanowska A, Mielczarek-Puta M, Joniec-Maciejak I, Słabik K, et al. Lactate formation in primary and metastatic colon cancer cells at hypoxia and normoxia. Cell Biochem Funct. 2016;34(7):483–90.CrossRef
30.
go back to reference Wang T, Cai G, Qiu Y, Fei N, Zhang M, Pang X, et al. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J. 2012;6(2):320–9.CrossRef Wang T, Cai G, Qiu Y, Fei N, Zhang M, Pang X, et al. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J. 2012;6(2):320–9.CrossRef
32.
go back to reference Companys J, Gosalbes MJ, Pla-Pagà L, Calderón-Pérez L, Llauradó E, Pedret A, et al. Gut microbiota profile and its association with clinical variables and dietary intake in overweight/obese and lean subjects: a cross-sectional study. Nutrients. 2021;13(6):2032.CrossRef Companys J, Gosalbes MJ, Pla-Pagà L, Calderón-Pérez L, Llauradó E, Pedret A, et al. Gut microbiota profile and its association with clinical variables and dietary intake in overweight/obese and lean subjects: a cross-sectional study. Nutrients. 2021;13(6):2032.CrossRef
33.
go back to reference Yan H, Qin Q, Chen J, Yan S, Li T, Gao X, et al. Gut microbiome alterations in patients with visceral obesity based on quantitative computed tomography. Front Cell Infect Microbiol. 2022;11: 823262.CrossRef Yan H, Qin Q, Chen J, Yan S, Li T, Gao X, et al. Gut microbiome alterations in patients with visceral obesity based on quantitative computed tomography. Front Cell Infect Microbiol. 2022;11: 823262.CrossRef
Metadata
Title
Metagenomic analysis of the interaction between the gut microbiota and colorectal cancer: a paired-sample study based on the GMrepo database
Authors
Han Chen
Jianhua Jiao
Min Wei
Xingzhou Jiang
Ruoyun Yang
Xin Yu
Guoxin Zhang
Xiaoying Zhou
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Gut Pathogens / Issue 1/2022
Electronic ISSN: 1757-4749
DOI
https://doi.org/10.1186/s13099-022-00527-8

Other articles of this Issue 1/2022

Gut Pathogens 1/2022 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.