Published online Sep 28, 2019. doi: 10.3748/wjg.v25.i36.5543
Peer-review started: July 3, 2019
First decision: August 2, 2019
Revised: September 2, 2019
Accepted: September 9, 2019
Article in press: September 9, 2019
Published online: September 28, 2019
An alterated status of the gut microbiota is usually responsible for a reduction of short chain fatty acids (SCFAs), the major metabolites produced by bacterial fermentation, that are essential in maintaining gut homeostasis. Different studies have documented an alteration in SCFAs’ composition in various human pathologies, that may reflect a dysbiotic condition affecting the healthy status.
The SCFAs’ determination in stool samples could provide a faster, reliable and cheaper method to highlight the presence of an intestinal dysbiosis. Anyway, the high heterogeneity of methods used for their determination (i.e., gas chromatography, high performance liquid chro-matography, nuclear magnetic resonance, capillary electrophoresis) make difficult to compare literature data and bringing out real differences in SCFAs’ profiles of various disorders. Indeed, the use of a standardized protocol for their evaluation is essential to understand if the fecal SCFAs signature could represent a potential biomarker in the clinical practice, for example for the detection of different gut diseases.
The main objective of this study was to compare the fecal SCFAs’ profile of patients with adenomatous polyposis (AP), celiac disease (CD) and colorectal cancer (CRC) to healthy controls (HC), applying the same protocols and analytical conditions gas chromatography-mass spectrometry (GC-MS) for their evaluation, in order to point out whether these pathologies displayed a particular fecal SCFAs signature.
In this cross-sectional study, we defined and compared the SCFAs’ concentration in fecal samples of 44 patients with different gut diseases (19 with CRC, 9 with AP, 16 with CD) and 16 healthy controls. The SCFAs’ analysis were performed using a GC-MS method. Data analysis was carried out using Wilcoxon rank-sum test to assess pairwise differences of SCFAs’ profiles, partial least squares-discriminate analysis (PLS-DA) to determine the status membership based on distinct SCFAs’ profiles, and Dirichlet regression to determine factors influencing concentration levels of SCFAs.
In our study, we have not observed any difference in the SCFAs’ amount and composition between CD and healthy control. On the contrary, the total amount of SCFAs was significantly lower in CRC patients compared to HC and CD. Moreover, the percentage of each SCFA changed in CRC and AP patients compared to HC. In particular, HC displayed a higher percentage of acetic acid and a lower amount of butyric, isobutyric, isovaleric and valeric acids compared to CRC patients. Regarding AP patients, they showed a lower abundance of acetic acid and higher percentages of propionic and isovaleric acids compared to HC. Moreover, the PLS-DA model performed on the SCFAs’ percentages matrix, confirmed that CRC and AP patients showed a distinct separation from the healthy subjects and were not coinciding. Overall the small sample size of this study does not allow us to reach definitive conclusions, and our findings remain exploratory.
In this study we have analyzed, for the first time, the fecal SCFAs’ profile of patients with different gut diseases (AP, CD and CRC) and healthy subjects, applying the same protocols and analytical conditions (GC-MS). Even if the small sample size of study does not allow us to reach definitive conclusions, our findings shown the existence of a fecal SCFAs fingerprint in patients with CRC, with a clear separation (with significant qualitative and quantitative differences) in the SCFAs’ composition, compared to healthy control. In addition, AP patients have showed a characteristic SCFAs’ profile, distinguishable from CRC and healthy subjects. On the contrary, no separation between celiac patients and healthy controls was obtained regarding the SCFAs’ composition profile. If confirmed in larger cohorts of patients, we think that the fecal SCFAs’ analysis through GC-MS could be considered as a noninvasive and reliable diagnostic marker for the detection of adenoma and CRC patients.
By comparing the fecal SCFAs signatures of different gut disease using the same analytical method, we realized the clinical and diagnostic potential of our preliminary result, suggesting the use of SCFAs as potential biomarker in adenomatous polyposis and colorectal cancer. In our future research we will enlarge the sample size of this study to confirm the specific fecal SCFAs fingerprints in CRC and AP, in order to develop a non-invasive diagnostic protocol to be used in gastrointestinal clinical practice. The best method for future research is to continue the comparison of fecal SCFA profile in cohorts of patients with different diseases, where the microbiota has been shown to be involved. Examining a statistically significant number of patients with the same protocol used in this study, will be crucial to reach definitive conclusions. If our result will be confirmed, the fecal SCFAs’ analysis through GC-MS could be proposed as an innovative, noninvasive and reliable diagnostic method for the detection of adenoma and CRC patients and, in future, for other pathologies.