Published online Oct 14, 2021. doi: 10.3748/wjg.v27.i38.6430
Peer-review started: March 9, 2021
First decision: May 1, 2021
Revised: May 17, 2021
Accepted: August 25, 2021
Article in press: August 25, 2021
Published online: October 14, 2021
Colorectal cancer (CRC) is globally the third most common cause of death. If diagnosed at an early stage, CRC shows a good response to therapy and usually a better prognosis. Unfortunately, despite its invasiveness, colonoscopy represents the gold-standard screening procedure for CRC.
Considering that colonoscopy is an expensive and invasive procedure, it seems to be essential to introduce custom-made methodologies combining minimal invasiveness, safety, and reproducibility. Fecal sample screening has many advantages with respect to other screening techniques.
The main objective of our study was to compare with HCs (HCs) the fecal nuclear magnetic resonance (NMR) metabolomic profiles of patients with CRC or adenomatous polyposis (AP) to characterize the variations among the groups and potentially identify some diagnostic markers.
In order to define the fecal metabolic profile of 32 CRC, 16 AP patients and 38 HCs we used proton nuclear magnetic resonance spectroscopy in combination with multivariate and univariate statistical approaches.
The NMR spectra of 86 fecal extract samples have been acquired. With the aim of identifying metabolite level variations characteristic for each group, univariate analyses were applied to the identified fecal metabolites. The most marked changes were observed in the metabolic profiles of fecal samples of CRC patient vs HCs. AP patients, compared to HCs show significant lower amount of 3-hydroxyphelylacetate, butyrate, acetate, propionate, isobutyrate and lactate+threonine. In CRC fecal extract profiles, when compared to AP patients, only leucine, tyrosine, and valine remained statistically significant and present in higher amounts.
The metabolic screening of stool samples might contribute to the development of non-invasive screening tests. To date, studies evaluating fecal metabolic changes associated with CRC are still lacking. Furthermore, no study has described fecal metabolomic changes associated with adenoma. The short-chain fatty acids were found to be significantly decreased in CRC and AP patients, and in particular, lower levels of acetate were observed with respect to HCs. In contrast with previous data, we did not find decreased levels of butyric acid in CRC patients compared to HCs; however, we observed significantly decreased levels in AP patients. We showed significantly low levels of 3-hydroxyphenylacetic (3-HPAA) acid in both CRC and AP patients. Finally, higher amounts of amino acids such as leucine, tyrosine, and valine were present in the stool of CRC patients (compared to AP), probably resulting from malabsorption due to large epithelial inflammation and damage.
For the first time, we showed that fecal sample profiles can discriminate among CRC patients, AP patients and HCs, and some discriminatory metabolites were identified including acetate, butyrate, propionate, 3-HPAA acid, valine, tyrosine, and leucine. We believe that our data will be a starting point for future studies on CRC management, especially the diagnostics and evaluation of the effective of the treatments.