Short-chain Fatty Acids In Blood Research Articles

Effects of Coenzyme Q10 on the Biomarkers (Hydrogen, Methane, SCFA and TMA) and Composition of the Gut Microbiome in Rats.

The predominant route of administration of drugs with coenzyme Q10 (CoQ10) is administration per os. The bioavailability of CoQ10 is about 2-3%. Prolonged use of CoQ10 to achieve pharmacological effects contributes to the creation of elevated concentrations of CoQ10 in the intestinal lumen. CoQ10 can have an effect on the gut microbiota and the levels of biomarkers it produces. CoQ10 at a dose of 30 mg/kg/day was administered per os to Wistar rats for 21 days. The levels of gut microbiota biomarkers (hydrogen, methane, short-chain fatty acids (SCFA), and trimethylamine (TMA)) and taxonomic composition were measured twice: before the administration of CoQ10 and at the end of the experiment. Hydrogen and methane levels were measured using the fasting lactulose breath test, fecal and blood SCFA and fecal TMA concentrations were determined by NMR, and 16S sequencing was used to analyze the taxonomic composition. Administration of CoQ10 for 21 days resulted in a 1.83-fold (p = 0.02) increase in hydrogen concentration in the total air sample (exhaled air + flatus), a 63% (p = 0.02) increase in the total concentration of SCFA (acetate, propionate, butyrate) in feces, a 126% increase in butyrate (p = 0.04), a 6.56-fold (p = 0.03) decrease in TMA levels, a 2.4-fold increase in relative abundance of Ruminococcus and Lachnospiraceae AC 2044 group by 7.5 times and a 2.8-fold decrease in relative representation of Helicobacter. The mechanism of antioxidant effect of orally administered CoQ10 can include modification of the taxonomic composition of the gut microbiota and increased generation of molecular hydrogen, which is antioxidant by itself. The evoked increase in the level of butyric acid can be followed by protection of the gut barrier function.

A Concise Review of Liquid Chromatography-Mass Spectrometry-Based Quantification Methods for Short Chain Fatty Acids as Endogenous Biomarkers.

Fatty acids are widespread naturally occurring compounds, and essential constituents for living organisms. Short chain fatty acids (SCFAs) appeared as physiologically relevant metabolites for their involvement with gut microbiota, immunology, obesity, and other pathophysiological functions. This has raised the demand for reliable analytical detection methods in a variety of biological matrices. Here, we describe an updated overview of sample pretreatment techniques and liquid chromatography-mass spectrometry (LC-MS)-based methods for quantitative analysis of SCFAs in blood, plasma, serum, urine, feces and bacterial cultures. The present review incorporates various procedures and their applications to help researchers in choosing crucial parameters, such as pretreatment for complex biological matrices, and variables for chromatographic separation and detection, to establish a simple, sensitive, and robust quantitative method to advance our understanding of the role of SCFAs in human health and disease as potential biomarkers.

Diet-Related Changes of Short-Chain Fatty Acids in Blood and Feces in Obesity and Metabolic Syndrome.

Obesity-related illnesses are one of the leading causes of death worldwide. Metabolic syndrome has been associated with numerous health issues. Short-chain fatty acids (SCFAs) have been shown to have multiple effects throughout the body, both directly as well as through specific G protein-coupled receptors. The main SCFAs produced by the gut microbiota are acetate, propionate, and butyrate, which are absorbed in varying degrees from the large intestine, with some acting mainly locally and others systemically. Diet has the potential to influence the gut microbial composition, as well as the type and amount of SCFAs produced. High fiber-containing foods and supplements increase the production of SCFAs and SCFA-producing bacteria in the gut and have been shown to have bodyweight-lowering effects. Dietary supplements, which increase SCFA production, could open the way for novel approaches to weight loss interventions. The aim of this review is to analyze the variations of fecal and blood SCFAs in obesity and metabolic syndrome through a systematic search and analysis of existing literature.

Enalapril Diminishes the Diabetes-Induced Changes in Intestinal Morphology, Intestinal RAS and Blood SCFA Concentration in Rats.

Evidence suggests that microbiota-derived metabolites, including short-chain fatty acids (SCFAs) and trimethylamine-oxide (TMAO), affect the course of diabetic multiorgan pathology. We hypothesized that diabetes activates the intestinal renin–angiotensin system (RAS), contributing to gut pathology. Twelve-week-old male rats were divided into three groups: controls, diabetic (streptozotocin-induced) and diabetic treated with enalapril. Histological examination and RT-qPCR were performed to evaluate morphology and RAS expression in the jejunum and the colon. SCFA and TMAO concentrations in stools, portal and systemic blood were evaluated. In comparison to the controls, the diabetic rats showed hyperplastic changes in jejunal and colonic mucosa, increased plasma SCFA, and slightly increased plasma TMAO. The size of the changes was smaller in enalapril-treated rats. Diabetic rats had a lower expression of Mas receptor (MasR) and angiotensinogen in the jejunum whereas, in the colon, the expression of MasR and renin was greater in diabetic rats. Enalapril-treated rats had a lower expression of MasR in the colon. The expression of AT1a, AT1b, and AT2 receptors was similar between groups. In conclusion, diabetes produces morphological changes in the intestines, increases plasma SCFA, and alters the expression of renin and MasR. These alterations were reduced in enalapril-treated rats. Future studies need to evaluate the clinical significance of intestinal pathology in diabetes.

Modeling of systemic inflammatory response syndrome by chemical induction of colon injury in rats

Our objective was to develop a model of systemic inflammatory response syndrome (SIRS) by chemical induction of colon injury and antibiotic-associated intestinal dysbiosis in rats with primary visceral obesity (PVO) for studies of myocardial resistance to ischemia-reperfusion injury. The experiments were performed with adult Wistar male rats with PVO under improved conditions of a conventional animal clinic. The chemically induced inflammatory colon disease (CIICD) was accomplished by intragastric administration of a mixture of broad-spectrum antimicrobial agents (AMA) for 3 days. Five days later, immunological and biochemical studies were carried out, as follows: composition of the intestinal microbiota in feces and shortchain fatty acids in blood, morphological changes in the structure of the colon, hemodynamic parameters and myocardial stability with modified Langendorff system. In PVO rats, the mass of visceral fat deposits and the content of lipopolysaccharides (LPS) in the blood were significantly increased when giving them fatcarbohydrate diet (FCD). In animals with CIICD, in addition to LPS, there was a significant increase in proinflammatory cytokine concentration (TNF, IL-8, MCP-1), and after oral administration of the AMA mixture, pronounced disturbances of food behavior and evacuatory function of gastrointestinal tract, deep destructive changes in colon, as well as qualitative and quantitative composition of intestinal microbiota with characteristics typical to the first-grade dysbiosis. High levels were shown for IL-8 cytokine only. An increase in acetic and propionic acid concentrations were shown in blood in animals with CIICD, and, to a greater extent, in rats with antibiotic-induced dysbiosis (AID). FCD was followed by significantly reduced levels of lactobacilli and bifidobacteria in colonic contents. CIICD leads to detection of Escherichia coli, and intestinal dysbiosis leads to the manifestation of Proteus. A comorbid combination of pathological changes in the immune and digestive systems caused a significant increase in the area of myocardial necrosis (by 35 percent) in isolated heart by, thus presuming decreased myocardial resistance to ischemia-reperfusion injury (IRI). The SIRS model induced by chemical trauma to large intestine is aggravated by the introduction of AMAs mixture, and it is characterized by a controlled change in inflammatory markers. Deterioration of morphofunctional characteristics in isolated heart included decrease in resistance to IRI seems to correspond to acute inflammatory bowel disease with induced intestinal dysbiosis. This model can be used in experimental medicine in the field of cardiology, endomicroecology, gastroenterology, and immunology.

Associations of gut microbiota, dietary intake, and serum short-chain fatty acids with fecal short-chain fatty acids.

In recent years, short-chain fatty acids (SCFAs) have been reported to play an important role in maintaining human health. Fecal SCFA concentrations correlate well with colonic SCFA status and gut microbiota composition. However, the associations with the gut microbiota functional pathway, dietary intake, blood SCFAs, and fecal SCFAs remain uncertain. To clarify these relationships, we collected fecal samples, blood samples, and dietary habit data from 12 healthy adults aged 22–51 years. The relative abundance of several SCFA-producing bacteria, gut microbiota diversity, and functional pathways related to SCFA biosynthesis were positively associated with fecal SCFAs even after adjusting for age and sex. Furthermore, fecal acetate was likely to be positively associated with serum acetate. By contrast, dietary intake was not associated with fecal SCFAs. Overall, the present study highlights the potential usefulness of fecal SCFAs as an indicator of the gut microbiota ecosystem and dynamics of SCFAs in the human body.

Determination of total, free and esterified short-chain fatty acid in human serum by liquid chromatography-mass spectrometry.

Short-chain fatty acids are primarily absorbed through the portal vein during lipid digestion, which is utilized as the energy source, as well as prevent type 2 diabetes and some cancers. However, reports on the determination of these short-chain fatty acids in human serum are limited. Blood samples from human subjects ( n = 547, male/female = 246/301, age 58.85 ± 12.57) were collected. Saponification was applied to obtain total fatty acid. After derivatization by 2-nitrophenylhydrazine, fatty acid 4:0 and fatty acid 6:0 were measured by liquid chromatography-mass spectrometry. The developed method exhibited good linearity (R2 = 0.9996 for both). All the coefficients of variation of reproducibility and accuracy for fatty acid 4:0 and fatty acid 6:0 ranged 3.0%-6.1%, with the average recoveries of 87.8%-102.4% and 92.2%-98.2%, respectively. In all the samples, the concentration of fatty acid 4:0 (162.4 ± 76.4 μmol/L) was significantly higher than fatty acid 6:0 (2.0 ± 2.5 μmol/L, P < 0.001). Furthermore, the esterified form was predominant in both fatty acid 4:0 and fatty acid 6:0 (98.2% and 82.4% of total fatty acids, respectively). Besides, short-chain fatty acids showed no significant differences with regard to sex or age differences. This developed liquid chromatography-mass spectrometry method is convenient and reliable, which might be useful for monitoring the variations of short-chain fatty acids in blood.

Quantification of Whole Blood Short-chain Fatty Acids by Gas Chromatographic Determination of Plasma 2-chloroethyl Derivatives and Correction for Dilution Space in Erythrocytes

A precise, accurate and stable method for quantification of short-chain fatty acids (SCFA) in ovine whole blood is presented and validated. The method is based on esterification of plasma SCFA by reaction with chloroethyl chloroformate in a water/acetonitrile/2-chloroethanol solution and gas chromatographic (GC) analysis of the derivatives. Whole blood concentrations of SCFA could be obtained by correcting plasma concentrations for a 45% dilution space of SCFA in the erythrocyte fraction of the blood. The recovery of SCFA in plasma and whole blood was 96-100% independent of the haematocrit value when compared with water standards. The method avoided carry-over from sample to sample, contrary to earlier published methods. The average intra-assay and inter-assay coefficient of variation for repeated measurement of SCFA content in plasma samples was 2.5% and 3.1%, respectively. The derivative was found to be suitable for a precise and accurate determination of the 13

Portal and peripheral blood short chain fatty acid concentrations after caecal lactulose instillation at surgery.

The major end products of fermentation, short chain fatty acids (acetate, propionate, butyrate) were measured in portal and peripheral venous blood after the caecal instillation of lactulose at surgery in patients undergoing elective cholecystectomy. Blood samples for short chain fatty acid measurement were taken before and at 15 minute intervals up to 60 minutes after caecal instillation of either 20 ml sterile saline or 6.7 g or 10 g lactulose. Fasting concentrations (n = 28) were (mumol/l, mean (SD)); portal acetate 128.0 (70.8), propionate 34.4 (23.3), butyrate 17.6 (18.4); peripheral acetate 67.0 (23.0), propionate 3.7 (1.2), butyrate traces only. After lactulose there was a rapid rise in portal short chain fatty acids with peak concentrations being reached in 15 to 45 minutes. Mean peak concentrations (mumol/l (SD)) after 10 g lactulose were acetate 240.9 (142.2), propionate 39.0 (17.8) and butyrate 26.9 (17.6). The changes in acetate concentrations seen in portal blood were reflected in peripheral blood acetate measurements. In contrast with portal blood, only small amounts of propionate and traces of butyrate were found in peripheral blood.

DEVELOPMENT AND DESIGN OF A LIQUID MEMBRANE ENZYME REACTOR FOR THE DETOXIFICATION OF BLOOD

Abstract Liver failure causes the enrichment of different lipophilic metabolites: phenol derivatives, mercaptans and short-chain fatty acids in blood. The removal of these toxines from blood is necessary to avoid death and to support the liver's self-regeneration. The liquid surfactant membrane technique with consecutive chemical reaction is used for this purpose. Liquid membranes were developed for the extraction of fatty acids. Enhancement of mass transfer is achieved by an instantaneous chemical reaction inside the emulsion globules, selectivity is obtained by using a suitable carrier. Essential fatty acids are not affected. Phenolic compounds are removed by extraction and consecutive enzymatic reaction inside the liquid membrane globules. This way of detoxification is identical with elimination in the living organism. Furthermore, a new model is being developed to describe the results of phenol extraction. This model makes possible the simulation of the detoxification process in the human organism. A ...