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

Le Gall G., Guttula K., Kellingray L., Tett A. J., ten Hoopen R., Kemsley E. K., Savva G. M., Ibrahim A., Narbad A.. (2018)

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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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