Evaluation and comparison of short chain fatty acids composition in gut diseases

Abstract

BACKGROUNDAn altered (dysbiosis) and unhealthy status of the gut microbiota is usually responsible for a reduction of short chain fatty acids (SCFAs) concentration. SCFAs obtained from the carbohydrate fermentation processes are crucial in maintaining gut homeostasis and their determination in stool samples could provide a faster, reliable and cheaper method to highlight the presence of an intestinal dysbiosis and a biomarker for various gut diseases. We hypothesize that different intestinal diseases, such as celiac disease (CD), adenomatous polyposis (AP) and colorectal cancer (CRC) could display a particular fecal SCFAs’ signature.AIMTo compare the fecal SCFAs’ profiles of CD, AP, CRC patients and healthy controls, using the same analytical method.METHODSIn this cross-sectional study, we defined and compared the SCFAs’ concentration in fecal samples of 9 AP, 16 CD, 19 CRC patients and 16 healthy controls (HC). The SCFAs’ analysis were performed using a gas-chromatography coupled with mass spectrometry 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.RESULTSWe 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 (P = 0.044) and CD (P = 0.005). Moreover, the SCFAs’ percentage composition was different in CRC and AP compared to HC. In detail, HC displayed higher percentage of acetic acid (P value = 1.3 × 10-6) and a lower amount of butyric (P value = 0.02192), isobutyric (P value = 7.4 × 10-5), isovaleric (P value = 0.00012) and valeric (P value = 0.00014) acids compared to CRC patients. AP showed a lower abundance of acetic acid (P value = 0.00062) and higher percentages of propionic (P value = 0.00433) and isovaleric (P value = 0.00433) acids compared to HC. Moreover, AP showed higher levels of propionic acid (P value = 0.03251) and a lower level of isobutyric acid (P value = 0.00427) in comparison to CRC. The PLS-DA model demonstrated a significant separation of CRC and AP groups from HC, although some degree of overlap was observed between CRC and AP.CONCLUSIONAnalysis of fecal SCFAs shows the potential to provide a non-invasive means of diagnosis to detect patients with CRC and AP, while CD patients cannot be discriminated from healthy subjects.

An Overview of Gut Microbiota and Colon Diseases with a Focus on Adenomatous Colon Polyps

“…Different studies have documented that an alteration of SCFAs in gut composition has also been associated with colorectal cancer, among other pathologies [ 146 , 147 ]. Changes in gut microbiota frequently cause a reduction in the concentration of SCFAs.…”

“…However, iso-butyric, valeric, and iso-valeric acids are also present in lower amounts. These fatty acids can provide energy through oxidative metabolism after entering the colonic epithelium, or they can aid in the regulation of the metabolism of fatty acids, glucose, and cholesterol upon entering the bloodstream [ 146 , 147 , 148 ].…”

Propionate supplementation promotes the expansion of peripheral regulatory T-Cells in patients with end-stage renal disease

“…It has been shown, that SCFA levels are lower in men compared to women, but so is the general dietary fiber intake, indicating that diet plays an important role [46]. Similarly, neither gender nor age were shown to be confounding factors in comparison of SCFA levels in various gut related illness [47]. However, the distribution of gender within the present cohort could to some degree obscure the true effect of propionic acid.…”

Significant and conflicting correlation of IL-9 withPrevotellaandBacteroidesin human colorectal cancer

“…indicating high genomic diversity of the different species 140 as well as a high differentiation among 513 strains of the same species, as for instance P. copri 141 . It is well documented that bacteria can 514 modulate the lymphocyte differentiation by the SCFAs (as previously 142 ), whose composition can 515 vary (qualitatively and quantitatively) based on the inflammatory status, as we have recently shown 516 for different intestinal gastrointestinal pathologies, such as celiac disease, adenomatous polyposis and 517 CRC 143 . Maybe the periodontal Prevotella spp.…”