Oncotarget

Research Papers:

Metabolite quantification of faecal extracts from colorectal cancer patients and healthy controls

Gwénaëlle Le Gall _, Kiran Guttula, Lee Kellingray, Adrian J. Tett, Rogier ten Hoopen, Kate E. Kemsley, George M. Savva, Ashraf Ibrahim, Arjan Narbad

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Oncotarget. 2018; 9:33278-33289. https://doi.org/10.18632/oncotarget.26022

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Abstract

Gwénaëlle Le Gall1,*, Kiran Guttula2,*, Lee Kellingray1,*, Adrian J. Tett3, Rogier ten Hoopen2, Kate E. Kemsley1, George M. Savva1, Ashraf Ibrahim2,* and Arjan Narbad1,*

1Quadram Institute Bioscience, Norwich Research Park, Norwich, UK

2Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK

3Centre for Integrative Biology, University of Trento, Trento, Italy

*These authors contributed equally to this work

Correspondence to:

Gwénaëlle Le Gall, email: gwenaelle.legalln@gmail.com

Keywords: NMR; colorectal cancer; markers; metabolite; metabolomics

Received: February 07, 2018     Accepted: August 10, 2018     Published: September 07, 2018

ABSTRACT

Colorectal cancer (CRC), a primary cause of morbidity and mortality worldwide is expected to rise in the coming years. A better understanding of the metabolic changes taking place during the disease progression is needed for effective improvements of screening strategies and treatments. In the present study, Nuclear Magnetic Resonance (NMR) metabolomics was used to quantify the absolute concentrations of metabolites in faecal extracts from two cohorts of CRC patients and healthy controls. The quantification of over 80 compounds revealed that patients with CRC had increased faecal concentrations of branched chain fatty acids (BCFA), isovalerate and isobutyrate plus valerate and phenylacetate but diminished concentrations of amino acids, sugars, methanol and bile acids (deoxycholate, lithodeoxycholate and cholate). These results suggest that alterations in microbial activity and composition could have triggered an increase in utilisation of host intestinal slough cells and mucins and led to an increase in BCFA, valerate and phenylacetate. Concurrently, a general reduction in the microbial metabolic function may have led to reduced levels of other components (amino acids, sugars and bile acids) normally produced under healthy conditions. This study provides a thorough listing of the most abundant compounds found in human faecal waters and presents a template for absolute quantification of metabolites. The production of BCFA and phenylacetate in colonic carcinogenesis warrants further investigations.


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