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A prospective analysis of mucosal microbiome-metabonome interactions in colorectal cancer using a combined MAS 1HNMR and metataxonomic strategy

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Title: A prospective analysis of mucosal microbiome-metabonome interactions in colorectal cancer using a combined MAS 1HNMR and metataxonomic strategy
Authors: Kinross, J
Mirnezami, R
Alexander, J
Brown, R
Scott, A
Galea, D
Veselkov, K
Goldin, R
Darzi, A
Nicholson, J
Marchesi, JR
Item Type: Journal Article
Abstract: Colon cancer induces a state of mucosal dysbiosis with associated niche specific changes in the gut microbiota. However, the key metabolic functions of these bacteria remain unclear. We performed a prospective observational study in patients undergoing elective surgery for colon cancer without mechanical bowel preparation (n = 18). Using 16 S rRNA gene sequencing we demonstrated that microbiota ecology appears to be cancer stage-specific and strongly associated with histological features of poor prognosis. Fusobacteria (p < 0.007) and ε- Proteobacteria (p < 0.01) were enriched on tumour when compared to adjacent normal mucosal tissue, and fusobacteria and β-Proteobacteria levels increased with advancing cancer stage (p = 0.014 and 0.002 respecitvely). Metabonomic analysis using 1H Magic Angle Spinning Nuclear Magnetic Resonsance (MAS-NMR) spectroscopy, demonstrated increased abundance of taurine, isoglutamine, choline, lactate, phenylalanine and tyrosine and decreased levels of lipids and triglycerides in tumour relative to adjacent healthy tissue. Network analysis revealed that bacteria associated with poor prognostic features were not responsible for the modification of the cancer mucosal metabonome. Thus the colon cancer mucosal microbiome evolves with cancer stage to meet the demands of cancer metabolism. Passenger microbiota may play a role in the maintenance of cancer mucosal metabolic homeostasis but these metabolic functions may not be stage specific.
Issue Date: 21-Aug-2017
Date of Acceptance: 7-Jul-2017
URI: http://hdl.handle.net/10044/1/50085
DOI: 10.1038/s41598-017-08150-3
ISSN: 2045-2322
Publisher: Nature Publishing Group
Journal / Book Title: Scientific Reports
Volume: 7
Issue: 7
Copyright Statement: © The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: Bowel & Cancer Research
Commission of the European Communities
Biotechnology and Biological Sciences Research Council (BBSRC)
Commission of the European Communities
National Institute of Health Research
Funder's Grant Number: N/A
305259
BB/L020858/1
634402
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
NMR-SPECTROSCOPY
COLON-CANCER
MICROENVIRONMENT
FUSOBACTERIUM
SIGNATURES
MODEL
Cluster Analysis
Colorectal Neoplasms
DNA, Bacterial
DNA, Ribosomal
Gastrointestinal Microbiome
Humans
Intestinal Mucosa
Magnetic Resonance Spectroscopy
Metabolome
Metabolomics
Metagenomics
Microbiota
Phylogeny
Prospective Studies
RNA, Ribosomal, 16S
Sequence Analysis, DNA
Intestinal Mucosa
Humans
Colorectal Neoplasms
DNA, Bacterial
DNA, Ribosomal
RNA, Ribosomal, 16S
Magnetic Resonance Spectroscopy
Cluster Analysis
Prospective Studies
Sequence Analysis, DNA
Phylogeny
Metabolomics
Metabolome
Metagenomics
Microbiota
Gastrointestinal Microbiome
Publication Status: Published
Article Number: ARTN 8979
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Department of Surgery and Cancer
Faculty of Medicine
Institute of Global Health Innovation