Journal ArticleDOI
Integrated metagenomic and metabolomic analysis reveals distinct gut-microbiome-derived phenotypes in early-onset colorectal cancer
Cheng Kong,Lei Liang,Guang Liu,Lutao Du,Yongzhi Yang,Jianqiang Liu,Debing Shi,Xinxiang Li,Yan-yan Ma +8 more
TLDR
The predictive model based on metagenomic, metabolomic and KO gene markers achieved a powerful classification performance for distinguishing EO-CRC from controls, suggesting that altered microbiome–metabolome interplay helps explain the pathogenesis of EO.CRC.Abstract:
Objective The incidence of early-onset colorectal cancer (EO-CRC) is steadily increasing. Here, we aimed to characterise the interactions between gut microbiome, metabolites and microbial enzymes in EO-CRC patients and evaluate their potential as non-invasive biomarkers for EO-CRC. Design We performed metagenomic and metabolomic analyses, identified multiomics markers and constructed CRC classifiers for the discovery cohort with 130 late-onset CRC (LO-CRC), 114 EO-CRC subjects and age-matched healthy controls (97 LO-Control and 100 EO-Control). An independent cohort of 38 LO-CRC, 24 EO-CRC, 22 LO-Controls and 24 EO-Controls was analysed to validate the results. Results Compared with controls, reduced alpha-diversity was apparent in both, LO-CRC and EO-CRC subjects. Although common variations existed, integrative analyses identified distinct microbiome–metabolome associations in LO-CRC and EO-CRC. Fusobacterium nucleatum enrichment and short-chain fatty acid depletion, including reduced microbial GABA biosynthesis and a shift in acetate/acetaldehyde metabolism towards acetyl-CoA production characterises LO-CRC. In comparison, multiomics signatures of EO-CRC tended to be associated with enriched Flavonifractor plauti and increased tryptophan, bile acid and choline metabolism. Notably, elevated red meat intake-related species, choline metabolites and KEGG orthology (KO) pldB and cbh gene axis may be potential tumour stimulators in EO-CRC. The predictive model based on metagenomic, metabolomic and KO gene markers achieved a powerful classification performance for distinguishing EO-CRC from controls. Conclusion Our large-sample multiomics data suggest that altered microbiome–metabolome interplay helps explain the pathogenesis of EO-CRC and LO-CRC. The potential of microbiome-derived biomarkers as promising non-invasive tools could be used for the accurate detection and distinction of individuals with EO-CRC.read more
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Small molecule metabolites: discovery of biomarkers and therapeutic targets
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Molecular Characteristics of Early-Onset Colorectal Cancer According to Detailed Anatomical Locations: Comparison With Later-Onset Cases
Tomotaka Ugai,Koichiro Haruki,Tabitha A. Harrison,Yin Cao,Conghui Qu,Andrew T. Chan,Peter J. Campbell,Naohiko Akimoto,Sonja I. Berndt,Hermann Brenner,C. D. Buchanan,Jenny Chang-Claude,Kenji Fujiyoshi,Steven Gallinger,Marc J. Gunter,Akihisa Hidaka,Michael Hoffmeister,Li Hsu,Mark A. Jenkins,Roger L. Milne,Victor Moreno,Polly A. Newcomb,Reiko Nishihara,Rish K. Pai,Lori C. Sakoda,Martha L. Slattery,Wei Sun,Efrat L. Amitay,Elizabeth Alwers,Stephen N. Thibodeau,Amanda E. Toland,Bethany Van Guelpen,Michael O. Woods,Syed H.E. Zaidi,John D. Potter,Marios Giannakis,Mingyang Song,Jonathan A. Nowak,Amanda I. Phipps,Ulrike Peters,Shuji Ogino +40 more
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Journal ArticleDOI
Intestinal bacteria and colorectal cancer: etiology and treatment
TL;DR: In this article , an overview of how host-bacteria interactions influence colorectal cancer development, how this knowledge may be utilized to diagnose or prevent CRC, and how the gut microbiome influences CRC treatment efficacy, including aspects of host mutational status, intra-tumoral microbial heterogeneity, transient infection, and cumulative influence of multiple carcinogenic bacteria after sequential or co-colonization.
Journal ArticleDOI
Considerations for peripheral blood transport and storage during large-scale multicentre metabolome research
James L. Alexander,Nicola J. Wyatt,Stephane Camuzeaux,Elena Chekmeneva,Beatriz Jiménez,Caroline Sands,H. Fuller,Panteleimon G. Takis,Tariq Ahmad,Jennifer A Doyle,Ailsa Hart,Peter M. Irving,Nicholas A. Kennedy,Charles Lee,James O. Lindsay,Rebecca E. McIntyre,Miles Parkes,Natalie J. Prescott,Tim Raine,Jack Satsangi,Richard A. Speight,Luke Jostins-Dean,Nick Powell,Julian Marchesi,Christopher J. Stewart,Christopher A. Lamb +25 more
TL;DR: In this article , the impact of sample collection, shipping and storage on circulating metabolites was assessed for colorectal cancer patients in the CDmetaRESPONSE precision medicine multicentre study.
Journal ArticleDOI
Gut microbiota in colorectal cancer development and therapy
Chi Chun Wong,Jun Yu +1 more
References
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Rebecca L. Siegel,Kimberly D. Miller,Ann Goding Sauer,Stacey A. Fedewa,Lynn F. Butterly,Lynn F. Butterly,Joseph C. Anderson,Joseph C. Anderson,Andrea Cercek,Robert A. Smith,Ahmedin Jemal +10 more
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The gut microbiota, bacterial metabolites and colorectal cancer
TL;DR: The relationship between diet, microbial metabolism and CRC is discussed and it is argued that the cumulative effects of microbial metabolites should be considered in order to better predict and prevent cancer progression.
Journal ArticleDOI
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Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society
Andrew M.D. Wolf,Elizabeth T. H. Fontham,Timothy R. Church,Christopher R. Flowers,Carmen Guerra,Samuel J. LaMonte,Ruth Etzioni,Matthew T. McKenna,Kevin C. Oeffinger,Ya Chen Tina Shih,Louise C. Walter,Kimberly S. Andrews,Otis W. Brawley,Durado Brooks,Stacey A. Fedewa,Deana Manassaram-Baptiste,Rebecca L. Siegel,Richard C. Wender,Robert A. Smith +18 more
TL;DR: This guideline update used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence.