Faeces are comprised of a wide array of metabolites arising from the circulatory system as well as the human microbiome. A global metabolite analysis (metabolomics) of faecal extracts offers the potential to uncover new compounds which may be indicative of the onset of bowel diseases such as colorectal cancer (CRC). To date, faecal metabolomics is still in its infancy and the compounds of low abundance present in faecal extracts poorly characterised. In this study, extracts of faeces from healthy subjects were profiled using a sensitive nanoflow-nanospray LC-MS platform which resulted in highly repeatable peak retention times (<2% CV) and intensities (<15% CV). Analysis of the extracts revealed wide coverage of the faecal metabolome including detection of low abundant signalling compounds such as sex steroids and eicosanoids, alongside highly abundant pharmaceuticals and tetrapyrrole metabolites. A small pilot study investigating differences in metabolomics profiles of faecal samples obtained from 7 CRC, 25 adenomatous polyp and 26 healthy groups revealed that secondary bile acids, conjugated androgens, eicosanoids, phospholipids and an unidentified haem metabolite were potential classes of metabolites that discriminated between the CRC and control sample groups. However, much larger follow up studies are needed to confirm which components of the faecal metabolome are associated with actual CRC disease rather than dietary influences. This study reveals the potential of nanospray-nanoflow LC-MS profiling of faecal samples from large scale cohort studies for uncovering the role of the faecal metabolome in colorectal disease formation.

School of Life Sciences University of Sussex Falmer Brighton BN1 9QG UK

School of Life Sciences University of Sussex Falmer Brighton BN1 9QG UK; School of Geography Earth and Environmental Sciences University of Birmingham Edgbaston B15 2TT UK

School of Pharmacy and Biomolecular Sciences University of Brighton Brighton BN2 4GJ UK

School of Pharmacy and Biomolecular Sciences University of Brighton Brighton BN2 4GJ UK; Department of Biology and Biochemistry University of Bath Bath BA2 7AY UK

Surgery Department 2nd Medical Faculty of Charles University and University Hospital Motol Prague Czech Republic

Sussex Cancer Centre Royal Sussex County Hospital Brighton BN2 5DA UK

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