Metabolites

Background/Objectives: Consuming apples regularly has positive effects on human health due to their anti-inflammatory and antioxidant properties, which have been associated with their phenolic composition. To enhance the bioactive properties of apple phenolic compounds, high-pressure processing (HPP) has been studied as a tool to improve their extraction during gastrointestinal digestion with the aim of increasing their bioaccessibility and the amount that reaches the colon unchanged, which can serve as substrates for bacterial fermentation. This study aimed to analyze the impact of an HPP-apple ingredient on the metabolism of human gut microbiota using an in vitro dynamic simulator of gastrointestinal digestion and colonic fermentation (GID-CF) that allowed us to study the three colon regions separately (ascending—AC; transverse—TC; and descending—DC). Methods: Apples were HPP-treated (400 MPa/5 min) and lyophilized to obtain an HPP-apple ingredient in powder form. A GID-CF was employed to study the continuous intake of the HPP-apple ingredient for 14 days at 37.5 g/day. Results: The HPP-apple ingredient produced a significant accumulation of phenolic metabolites mainly in the DC, with benefits on human health. The main phenolic metabolites formed were phloroglucinol, 4-hydroxyphenylacetic acid, 4-hydroxy-3-methoxyphenylacetic acid, 3-(3-hydroxyphenyl)-propionic acid, and 3-(4-hydroxyphenyl)-propionic acid. A PCA revealed a perfect separation of the three colon regions based on the phenolic precursors and metabolites. The microbiota-modulatory effects were attributed to the increase in Bifidobacterium spp. and Lactobacillus spp. populations and the butyric acid (SCFA) concentration. Conclusions: The results obtained highlight the health benefits and potential prebiotic-like effect of the HPP-apple ingredient on the gut microbiota.

Background: Pathogenesis of aortic stenosis (AS) involves lipid infiltration, inflammation, and oxidative stress, which drive calcification of the aortic valve and progression to heart failure (HF). Fatty acids (FAs) play a crucial role in these processes. A treatment option for severe symptomatic AS in elderly and high-risk patients is transcatheter aortic valve implantation (TAVI). Objective: To investigate the change in FA profiles in patients undergoing TAVI. Methods: This single-center prospective study included 25 patients with severe AS qualified for TAVI procedure. Blood samples were collected before TAVI and after six months. FA profiles were analyzed by gas chromatography-electron ionization mass spectrometry. Results: Notable changes were identified in FA profiles, including a reduction in docosahexaenoic acid (DHA) levels (117 ± 48.0 µM vs. 141 ± 53.0 µM, p = 0.001) and an increase in alpha-linolenic acid (ALA) concentration (32.8 ± 12.3 µM vs. 19.9 ± 6.40 µM, p = 0.003) six months post-TAVI. Additionally, significant elevations were noted in specific medium-chain FAs (C12) and branched-chain fatty acids (iso C16, iso C17 and anteiso C15, anteiso C17) at six months after TAVI. However, total n-3 polyunsaturated fatty acids (n3 PUFA) levels decreased (p = 0.039), while n-6 polyunsaturated fatty acids (n6 PUFA) levels exhibited no significant overall change at this time point. Decrease in mean pressure gradient (PG) was negatively correlated with eicosapentaenoic acid (EPA), DHA, n-3 docosapentaenoic acid (DPA n3) and n3 PUFA levels in a six-month observation. Conclusions: Our results underscore the complex interplay between cardiac intervention and FA changes, providing novel insights into the metabolic impact of TAVI on FAs serum profile.

Introduction: The proteasome is a multicatalytic complex responsible for protein degradation and regulation of immune responses, and has been implicated in type 1 diabetes mellitus (T1DM) pathogenesis. Zinc (Zn²⁺) is essential for insulin granule biogenesis and modulates proteasomal activity. This study investigated associations between single-nucleotide polymorphisms (SNPs) in proteasomal subunits predicted to bind Zn²⁺ and T1DM susceptibility or related traits. Methods: This case–control study included 654 patients with T1DM and 573 subjects without DM from Southern Brazil. SNPs were selected through in silico analysis using MIB docking platform to identify Zn²⁺-interacting residues in proteasomal subunits. Five SNPs in proteasomal subunit genes—PSMA6 (rs1048990), PSMB6 (rs2304975), PSMB9 (rs17587), PSMC6 (rs2295825), and PSMD3 (rs3087852)—were genotyped using TaqMan assays. Results: The PSMC6 rs2295825C allele was associated with lower T1DM (OR = 0.77, 95% CI 0.61–0.97; p = 0.028) and diabetic retinopathy (DR; OR = 0.65; 95% CI 0.42–0.99; p = 0.048) risk, and a more favorable lipid profile (higher HDL-C, lower triglycerides) compared to the G/G genotype. The PSMB9 rs17587A/A genotype was linked to higher total cholesterol and HbA1c levels. The PSMA6 rs1048990G allele was linked to increased prevalence of diabetic kidney disease (DKD; OR = 1.75, 95% CI 1.02–2.99; p = 0.042), and the PSMD3 rs3087852A allele was associated with lower urinary albumin excretion. No significant associations were observed for the PSMB6 rs2304975 SNP. Conclusions: The PSMC6 rs2295825 SNP may confer protection against T1DM. The PSMC6 rs2295825, PSMB9 rs17587, PSMA6 rs1048990, and PSMD3 rs3087852 SNPs appear to influence lipid metabolism and diabetic microvascular complications.