Free Fatty Acids Signature in Human Intestinal Disorders: Significant Association between Butyric Acid and Celiac Disease

Abstract

Altered circulating levels of free fatty acids (FFAs), namely short chain fatty acids (SCFAs), medium chain fatty acids (MCFAs), and long chain fatty acids (LCFAs), are associated with metabolic, gastrointestinal, and malignant diseases. Hence, we compared the serum FFA profile of patients with celiac disease (CD), adenomatous polyposis (AP), and colorectal cancer (CRC) to healthy controls (HC). We enrolled 44 patients (19 CRC, 9 AP, 16 CD) and 16 HC. We performed a quantitative FFA evaluation with the gas chromatography–mass spectrometry method (GC–MS), and we performed Dirichlet-multinomial regression in order to highlight disease-specific FFA signature. HC showed a different composition of FFAs than CRC, AP, and CD patients. Furthermore, the partial least squares discriminant analysis (PLS-DA) confirmed perfect overlap between the CRC and AP patients and separation of HC from the diseased groups. The Dirichlet-multinomial regression identified only strong positive association between CD and butyric acid. Moreover, CD patients showed significant interactions with age, BMI, and gender. In addition, among patients with the same age and BMI, being male compared to being female implies a decrease of the CD effect on the (log) prevalence of butyric acid in FFA composition. Our data support GC–MS as a suitable method for the concurrent analysis of circulating SCFAs, MCFAs, and LCFAs in different gastrointestinal diseases. Furthermore, and notably, we suggest for the first time that butyric acid could represent a potential biomarker for CD screening.

High-Fructose Diet Alters Intestinal Microbial Profile and Correlates with Early Tumorigenesis in a Mouse Model of Barrett’s Esophagus

“…In targeted metabolomic analyses, we further examined SCFA levels in stool and serum of the mice. SCFAs are the main metabolites produced by bacterial anaerobic fermentation of unabsorbed carbohydrates, dietary fiber, and proteins in the colon [74][75][76]. SCFAs function as systemic energy substrates with distinct metabolic roles [75].…”

How Metabolomics Provides Novel Insights on Celiac Disease and Gluten-Free Diet: A Narrative Review

“…Based on GC–MS analysis, no significant differences emerged allowing the authors to conclude that short-chain fatty acids (SCFAs) in stools did not discriminate between enrolled groups. Subsequently, serum from both groups previously enrolled ( Niccolai et al, 2019 ) was processed by the same research group ( Baldi et al, 2021 ). Following the same GC–MS-based methodological approach, the authors found that U-CD patients had a lower relative concentration of circulating acetic, propionic, and valeric acids than HC.…”

“…Di Cagno et al (2009) found a critical lower concentration of total SCFAs in U-CD when compared to HC, while subjects who undertook GFD (T-CD) did not exhibit the same behavior. Contrarily, other studies reported the complete absence of differences in the levels of total SCFAs (Primec et al, 2016;Niccolai et al, 2019;Zafeiropoulou et al, 2020) or their increase (Tjellström et al, 2010;Nistal et al, 2012;Caminero et al, 2015;Baldi et al, 2021). The adoption of different methods (GC-or LC-MS), sample type (serum or feces), or data elaboration (absolute or relative concentration) could have led to these controversial results.…”

Effects of viremia and CD4 recovery on gut “microbiome-immunity” axis in treatment-naïve HIV-1-infected patients undergoing antiretroviral therapy

“…Each sample was prepared and processed, by the method described above, three times. In addition, serum FFAs, classified as SCFAs (acetic, propionic, butyric, isobutyric isovaleric, 2-methylbutyri, and valeric acids), medium chain fatty acids (MCFAs; hexanoic, heptanoic, octanoic, nonanoic, decanoic, and dodecanoic acids), and long chain fatty acids (LCFAs; tetradecanoic, hexadecanoic, and octadecanoic acids) were analyzed with our previous described GC-MS protocol[ 44 ]. The chemicals, GC-MS conditions, GC-MS method, and calibrations parameters are reported in supporting information (Tables S5-S7).…”