Background: Several approaches have been suggested to be useful in the early detection of colorectal neoplasms. Since metabolites are closely related to the phenotype and are available from different human bio-fluids, metabolomics are candidates for non-invasive early detection of colorectal neoplasms. Objectives: We aimed to summarize current knowledge on performance characteristics of metabolomics biomarkers that are potentially applicable in a screening setting for the early detection of colorectal neoplasms. Design: We conducted a systematic literature search in PubMed and Web of Science and searched for biomarkers for the early detection of colorectal neoplasms in easy-to-collect human bio-fluids. Information on study design and performance characteristics for diagnostic accuracy was extracted. Results: Finally, we included 41 studies in our analysis investigating biomarkers in different bio-fluids (blood, urine, and feces). Although single metabolites mostly had limited ability to distinguish people with and without colorectal neoplasms, promising results were reported for metabolite panels, especially amino acid panels in blood samples, as well as nucleosides in urine samples in several studies. However, validation of the results is limited. Conclusions: Panels of metabolites consisting of amino acids in blood and nucleosides in urinary samples might be useful biomarkers for early detection of advanced colorectal neoplasms. However, to make metabolomic biomarkers clinically applicable, future research in larger studies and external validation of the results is required.

Background Metabolomics analysis of human stool samples is of great interest for a broad range of applications in biomedical research including early detection of colorectal neoplasms. However, due to the complexity of metabolites there is no consensus on how to process samples for stool metabolomics measurements to obtain a broad coverage of hydrophilic and hydrophobic substances. Methods We used frozen stool samples (50 mg) from healthy study participants. Stool samples were processed after thawing using eight different processing protocols and different solvents (solvents such as phosphate-buffered saline, isopropanol, methanol, ethanol, acetonitrile and solvent mixtures with or without following evaporation and concentration steps). Metabolites were measured afterwards using the MxP Quant 500 kit (Biocrates). The best performing protocol was subsequently applied to compare stool samples of participants with different dietary habits. Results In this study, we were able to determine up to 340 metabolites of various chemical classes extracted from stool samples of healthy study participants with eight different protocols. Polar metabolites such as amino acids could be measured with each method while other metabolite classes, particular lipid species (better with isopropanol and ethanol or methanol following a drying step), are more dependent on the solvent or combination of solvents used. Only a small number of triglycerides or acylcarnitines were detected in human faeces. Extraction efficiency was higher for protocols using isopropanol (131 metabolites>limit of detection (LOD)) or those using ethanol or methanol and methyl tert-butyl ether (MTBE) including an evaporation and concentration step (303 and 342 metabolites>LOD, respectively) than for other protocols. We detected significant faecal metabolite differences between vegetarians, semivegetarians and non-vegetarians. Conclusion For the evaluation of metabolites in faecal samples, we found protocols using solvents like isopropanol and those using ethanol or methanol, and MTBE including an evaporation and concentration step to be superior regarding the number of detected metabolites of different chemical classes over others tested in this study.

Analysis of metabolomics has been suggested as a promising approach for early detection of colorectal cancer and advanced adenomas. We investigated and compared the metabolomics profile in blood, stool, and urine samples of screening colonoscopy participants and aimed to evaluate differences in metabolite concentrations between people with advanced colorectal neoplasms and those without neoplasms. Various types of bio-samples (plasma, feces, and urine) from 400 participants of screening colonoscopy were investigated using the MxP^® Quant 500 kit (Biocrates, Innsbruck, Austria). We detected a broad range of metabolites in blood, stool, and urine samples (504, 331, and 131, respectively). Significant correlations were found between concentrations in blood and stool, blood and urine, and stool and urine for 93, 154, and 102 metabolites, of which 68 (73%), 126 (82%), and 39 (38%) were positive correlations. We found significant differences between participants with and without advanced colorectal neoplasms for concentrations of 123, 49, and 28 metabolites in blood, stool and urine samples, respectively. We detected mostly positive correlations between metabolite concentrations in blood samples and urine or stool samples, and mostly negative correlations between urine and stool samples. Differences between subjects with and without advanced colorectal neoplasms were found for metabolite concentrations in each of the three bio-fluids.