Valeric Research Articles

Weizmannia coagulans BC99 affects valeric acid production via regulating gut microbiota to ameliorate inflammation and oxidative stress responses in Helicobacter pylori mice

AbstractHelicobacter pylori is a highly prevalent pathogen in human gastric mucosa epithelial cells with strong colonization ability. Weizmannia coagulans is a kind of active microorganism that is beneficial to the improvement of host gut microbiota balance and can prevent and treat intestinal diseases. We investigated the beneficial effects of W. coagulans BC99 in H. pylori infected mice and measured inflammation response, oxidative stress, and gut microbiota. Results showed that BC99 could alleviate the gastric inflammation, inhibit the increasing of inflammation parameters endotoxin, interleukin‐10, transforming growth factor‐β, and interferon‐γ and oxidative stress myeloperoxidase and malondialdehyde, promote the levels of superoxide dismutase and catalase. Furthermore, 16S rRNA gene sequencing analysis revealed that BC99 reversed the change of gut microbiota by reducing the abundance of Olsenella, Candidatus_Saccharimonas, Monoglobus, and increasing the abundance of Tyzzerella. Meanwhile, BC99 caused elevated levels of Ligilactobacillus and Lactobacillus. In view of the beneficial effect of BC99 on the content of short‐chain fatty acid, valeric acid with sodium valerate interfered with H. pylori infection in mice found that valeric acid had a good restorative effect of H. pylori infection relating inflammation and oxidative stress responses. These results suggest that W. coagulans BC99 can be used as a potential probiotic to prevent and treat H. pylori infection by regulating the inflammation, oxidative stress, and gut microbiota.

Effect of Dietary Xylanase Inclusion on Growth Performance, Nutrient Digestibility, and Digesta Viscosity of Weaned Pigs Fed Wheat–Soybean Meal-Based Diets

(1) Background: This study aimed to evaluate the effects of dietary xylanase addition on growth performance, nutrient digestibility, volatile fatty acids, and digesta viscosity at different digestive sites in weaned pigs fed wheat–soybean meal-based diets with reduced metabolizable energy. (2) Methods: A total of 312 weaned pigs (5.1 ± 0.9 kg, 20 ± 2 days of age) were assigned to one of six dietary treatments. The experimental diets were formulated in a three-phase nursery feeding program: phase 1 (d0–d7), phase 2 (d8–d21), and phase 3 (d22–d42). The experimental diets consisted of a wheat–soybean meal-based diet formulated to meet pig requirements (positive control, PC); the PC diet with a reduction of 100 kcal of metabolizable energy (ME) (negative control, NC); and the NC diet with either 900, 1800, 3600, or 7200 units of xylanase. Feed disappearance and body weight were measured at d7, 14, 21, and 42 in the nursery phase. The pen fecal score was assessed daily from d0 to d14 and three times a week from d15 to d28. On d21–d24 of the experiment (12 pigs per day), one pig per pen was selected for sample collection: ileal, cecal, and mid-colon digesta for viscosity and ileal digesta, feces for nutrient digestibility, and feces and cecal digesta for the measurement of volatile fatty acid. (3) Results: The addition of xylanase to the NC diets did not improve pig growth performance (body weight, feed conversion ratio, and average daily gain; p > 0.10) during the entire nursery phase. In Week 2 and Week 3, pigs fed xylanase had a lower (χ2 < 0.05) incidence of fecal scores 3 and 4 (diarrhea) than the PC and NC diets. In addition, the apparent total tract digestibility of neutral detergent fiber and acid detergent fiber increased linearly (p < 0.1) in response to xylanase addition. Xylanase addition (900 to 7200 U) decreased digesta viscosity in the colon compared to the PC and NC diets. Furthermore, xylanase addition resulted in a lower (p < 0.05) concentration of acetic, propionic, butyric, valeric, and total volatile fatty acid in cecal samples compared to PC. The addition of xylanase resulted in greater acetic and valeric acid concentrations in cecal samples compared to the NC group (p < 0.10). (4) Conclusions: Xylanase addition can improve nutrient digestibility, particularly at the total tract level, and reduce viscosity in the hindgut, which could be related to decreasing the occurrence of looseness. However, its impact on growth performance was minimal in wheat–soybean meal-based diets with a reduction of 100 kcal of ME.

Abstract 4134707: Metabolomics Discovery and Epicardial Adipose Tissue : a PROMISE Clinical Trial Substudy

Introduction: Epicardial adipose tissue (EAT) is a metabolically active tissue associated with cardiometabolic disease. EAT likely has local paracrine inflammatory and atherogenic effects on coronary vessels, but the metabolic underpinnings related to systemic metabolic pathways has not been evaluated. Hypothesis: We hypothesized that metabolic markers of lipid and fatty acid oxidation will be positively associated with volume of EAT. Methods: In a biomarker substudy of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) clinical trial which randomized participants to computed tomography angiography (CTA) vs. stress testing, we analyzed 1542 participants randomized to the CTA arm with available plasma at baseline. CTA phenotyping of EAT volume indexed to body surface area (cm 3 /m 2 ) was determined using a validated deep-learning algorithm. Comprehensive metabolomic profiling was performed on plasma samples using mass spectrometry. Principal components analysis (PCA) was used for dimensionality reduction of 571 named metabolites. Linear regression tested the association of metabolomic factors with EAT. Univariate models were adjusted for multiple comparisons and multivariate models were adjusted for age, race and ethnicity, sex, diabetes, BMI, LDL-C, HDL-C and metabolic syndrome. Results: Of 82 PCA-derived metabolomic factors, 16 were associated with EAT in univariate models and nine were associated with EAT in multivariate models (p=0.001-0.046); 116 individual metabolites heavily loaded within these factors were significantly associated with EAT volume in multivariate models ( Figure 1 ). This included three linoleic acid derivatives, six cholesterol esters, and glycine that were inversely associated with EAT volume (p<0.04) and 106 metabolites positively associated with EAT volume including di- and triacylcerols, glycerophospholipids, fatty acyls and dimethylguanidino valeric acid (p<0.05). Conclusions: Leveraging a large clinical trial of CTA to study metabolomics of EAT, we have identified circulating lipid species associated with EAT independent of BMI and conventional lipids. These findings highlight biomarkers of systemic metabolic dysregulation as risk modifiers and therapeutic targets in cardiometabolic disease prevention and treatment.

The association between circulating short-chain fatty acids and blood pressure in Chinese elderly population

The gut microbiome primarily generates short-chain fatty acids (SCFAs) by fermenting dietary fibers. Though previous studies have linked SCFAs to blood pressure, there remains a lack of research on the relationship between SCFAs levels in the serum of elderly individuals and blood pressure. Based on this, we investigated the associations of serum SCFAs with blood pressure in Chinese older adults in a cross-sectional study. In this report, we recruited 1013 older adults over 60 years of age from June to September 2016 in Lu 'an City, China. Using Ultra High Performance Liquid Chromatography-Quadrupole-Exactive-Orbitrap-Mass Spectrometry (UHPLC-QE-Orbitrap MS), we measured the level of various SCFAs, including acetic acid (AA), propanoic acid (PA), butyric acid (BA), isobutyric acid (iso-BA), valeric acid (VA), isovaleric acid (iso-VA), and caproic acid (CA), in serum samples collected from Chinese elderly adults. The study recruited 1013 older adults in total. Multiple logistic regression analysis shows that AA (OR = 0.696, 95%CI: 0.501–0.966) and VA (OR = 0.713, 95%CI: 0.516–0.985) are negatively associated with hypertension. Linear regression analysis shows a negative correlation between AA (β = -3.89, 95% CI: -7.12 – -0.66) and the systolic blood pressure (SBP) levels, and a significant negative association between iso-VA (β = -2.11, 95% CI: -3.94 – -0.29) and diastolic blood pressure (DBP) levels. Whether in unadjusted or adjusted linear regression models, we all observe significant positive associations between CA and blood pressure levels. In the Bayesian kernel-machine regression (BKMR) models, the trends between the mixture of SCFAs and hypertension, SBP are inverse, but not significant; we also observe a significant negative correlation between AA and SBP, and a significant negative association between iso-VA and DBP levels, while CA is significantly positively correlated with SBP and DBP. Collectively, our results advocate for considering SCFA as a potential intervention to lower blood pressure, and especially AA may be a possible target for research. This may provide new perspectives for understanding the role of SCFAs in hypertension.

Effects of moringa polysaccharides on growth performance, immune function, rumen morphology, and microbial community structure in early-weaned goat kids

The aim of this research was to investigate the effects of adding moringa polysaccharides (MOP) on the growth performance, immune function, rumen tissue morphology, and rumen microbial community in early-weaned goat kids. Twenty-one 7-day-old Leizhou male goat kids weighing (3.05 ± 0.63) kg, were randomly divided into a control group (CON group), a low-dose group (LOW group), and a high-dose group (HIG group). MOP was added to the goat kids’ milk replacer (MR) at 0, 0.15, and 0.3% (on dry matter basis),fed until 60 days of age, and four goat kids in each group with body weights close to the mean of each group were selected for slaughter. The results showed that, compared to the CON group, the MOP groups significantly improved final body weight, body measurements, daily weight gain, and feed intake of the early weaned goat kids; significantly reduced the content of propionic acid, butyric acid, valeric acid, and ammoniacal nitrogen; and in addition, the addition of MOP could significantly increase the height of rumen nipple, the content of immunoglobulin G (IgG) in the serum. The HIG group significantly increased rumen pH, rumen muscularis layer thickness, rumen wall thickness, and serum immunoglobulin A (IgA), and immunoglobulin M (IgM). In conclusion, the addition of MOP positively impacted the growth performance, serum immune function, and rumen tissue morphology in early-weaned goat kids.

Olfactory Dysfunction and Limbic Hypoactivation in Temporal Lobe Epilepsy.

The epileptogenic network in temporal lobe epilepsy (TLE) contains structures of the primary and secondary olfactory cortex such as the piriform and entorhinal cortex, the amygdala, and the hippocampus. Olfactory auras and olfactory dysfunction are relevant symptoms of TLE. This study aims to characterize olfactory function in TLE using olfactory testing and olfactory functional magnetic resonance imaging (fMRI). We prospectively enrolled 20 individuals with unilateral TLE (age 45 ± 20 years [mean ± SD], 65% female, 90% right-handed) and 20 healthy individuals (age 33 ± 15 years [mean ± SD], 35% female, 90% right-handed). In the TLE group, the presumed seizure onset zone was left-sided in 75%; in 45% of the individuals with TLE limbic encephalitis was the presumed etiology; and 15% of the individuals with TLE reported olfactory auras. Olfactory function was assessed with a Screening Sniffin' Sticks Test (Burkhart, Wedel, Germany) during a pre-assessment. During a pre-testing, all individuals were asked to rate the intensity, valence, familiarity, and associated memory of five different odors (eugenol, vanillin, phenethyl alcohol, decanoic acid, valeric acid) and a control solution. During the fMRI experiment, all individuals repeatedly smelled eugenol (positively valenced odor), valeric acid (negatively valenced odor), and the control solution and were asked to rate odor intensity on a five-point Likert scale. We acquired functional EPI sequences and structural images (T1, T2, FLAIR). Compared to healthy individuals, individuals with TLE rated the presented odors as more neutral (two-sided Mann-Whitney U tests, FDR-p < 0.05) and less familiar (two-sided Mann-Whitney U tests, FDR-p < 0.05). fMRI data analysis revealed a reduced response contrast in secondary olfactory areas (e.g., hippocampus) connected to the limbic system when comparing eugenol and valeric acid in individuals with TLE when compared with healthy individuals. However, no lateralization effect was obtained when calculating a lateralization index by the number of activated voxels in the olfactory system (two-sided Mann-Whitney U test; U = 176.0; p = 0.525). TLE is characterized by olfactory dysfunction and associated with hypoactivation of secondary olfactory structures connected to the limbic system. These findings contribute to our understanding of the pathophysiology of TLE. This study was preregistered on OSF Registries (www.osf.io).

A novel label-free impedance biosensor for KRAS G12C mutations detection based on PET-RAFT and ROP synergistic signal amplification

The KRAS G12C mutations, as crucial biomarkers, are closely associated with non-small cell lung cancer. Here, a novel label-free electrochemical biosensor with synergistic signal amplification of photocell energy transfer-reversible addition fragmentation chain transfer (PET-RAFT) and ring-opening polymerization (ROP) was developed for the first time for sensitive detection of KRAS G12C mutations. Specifically, hairpin DNA (hDNA), which act as biomolecular probe, was self-assembled on Au electrode surface by Au-S bond. 4-cyano-4-[(dodecylsulfanylthiocarbonyl) sulfanyl] pentanoic acid (CDTPA), the chain transfer agent of PET-RAFT reaction, was then attached to hDNA via amide bond. After that, the target DNA (tDNA) was captured on the electrode surface by complementary base pairing with hDNA. Subsequently, large numbers of electro-active monomers N-acryloxysuccinimide (NAS) were successfully grafted to the electrode surface via PET-RAFT reaction, which provided plenty of junction sites for doxorubicin-polycaprolactone (Dox-PCL) synthesized by ROP. Finally, the Dox-PCL was connected to the electrode surface by ester bond, significantly amplifying the electrochemical signal. Under optimized conditions, the biosensor has a wide linear detection range of 0.1 pM to 1 μM, with a detection limit of 86.9 fM. Attribute to its high sensitivity, specificity, reproducibility and stability, this biosensor possesses considerable potential in early diagnosis of disease and biomedical research.

Symmetric dimethylguanidino valeric acid (SDGV), a novel single biomarker of hepatic steatosis

Symmetric dimethylguanidino valeric acid (SDGV), a novel single biomarker of hepatic steatosis

Doubly Homologated Tyrosine-Containing Peptides from the Cyanobacterium Microcystis aeruginosa NIES-4285 and Their Biosynthesis.

Chemical investigation of the cyanobacterium Microcystis aeruginosa NIES-4285 led to the isolation of six new natural products, microginins 705 (1), 719 (2), 733A (3), 733B (4), and 733C (5), and anabaenopeptin 885 (7), and three known compounds, anabaenopeptins 871 (6), B (8), and F (9). Planar structures and absolute configurations for 1-7 were determined by 2D NMR, HRMS, and Marfey's analyses. Microginin 733C (5), and anabaenopeptins 871 (6) and 885 (7) contained a unique residue of 2-amino-5-(4-hydroxyphenyl)pentanoic acid (Ahppa): doubly homologated tyrosine (di-hTyr). The biosynthetic origin of this nonproteinogenic amino acid di-hTyr was investigated, and it was found that MaHphABCDE are involved in the production of di-hTyr. In addition, biochemical characterization of aminotransferase MaHphE showed that it is a promiscuous enzyme. This result expanded the biocatalytic toolbox for amino acid homologation.

Comparison of Conjugates Obtained Using DMSO and DMF as Solvents in the Production of Polyclonal Antibodies and ELISA Development: A Case Study on Bisphenol A

When developing immunochemical test systems, it is necessary to obtain specific antibodies. Their quality depends, among other things, on the immunogen used. When preparing hapten–protein conjugates to obtain antibodies for low-molecular-weight compounds, the key factors are the structure of the hapten itself, the presence of a spacer, the size of the carrier protein and the degree of its modification by hapten molecules. This work shows that one additional factor—the conditions for obtaining the hapten–protein conjugate—is overlooked. In this work, we have synthesized conjugates of bisphenol A derivative 4,4-bis(hydroxyphenyl)valeric acid (BVA), the protein carrier soybean trypsin inhibitor (STI), and bovine serum albumin (BSA) in reaction media combining water with two organic solvents: dimethylformamide (DMF) or dimethyl sulfoxide (DMSO). Namely, BSADMF–BVA, STIDMF–BVA, BSADMSO–BVA and STIDMSO–BVA conjugates were obtained. Rabbit polyclonal antibodies against the BSADMF–BVA conjugate demonstrated basically different interactions in the developed ELISA systems using either STIDMF–BVA or STIDMSO–BVA conjugates. The use of the STIDMF–BVA conjugate demonstrated the absence of competition in combination with antisera obtained from BSADMF–BVA in an ELISA. A competitive interaction was observed only with the use of the STIDMSO–BVA conjugate. Under the selected conditions, the detection limit of bisphenol A was 8.3 ng/mL, and the working range of determined concentrations was 18.5–290.3 ng/mL. The obtained data demonstrate the possibility of achieving sensitive immunoassays by simply varying the reaction media for the hapten–protein conjugation, which could provide an additional tool in the development of immunoassays for other low-molecular-weight compounds.

Ameliorating Effects of Nardostachys Jatamansi And Valeric Acid On Alcohol Withdrawal Induced Anxiety In Wistar Albino Rats.

Ameliorating Effects of Nardostachys Jatamansi And Valeric Acid On Alcohol Withdrawal Induced Anxiety In Wistar Albino Rats.

A Mix of Probiotic Strains Prevents Hepatic Steatosis, and Improves Oxidative Stress Status and Gut Microbiota Composition in Obese Mice.

The gut microbiota plays a role in fat accumulation and energy homeostasis. Therefore, probiotic supplementation may improve metabolic parameters and control body weight. In this study, mice are fed either a high-fat diet (HFD) or an HFD supplemented with oral gavage of a mixture of three probiotic strains, Bifidobacterium lactis Lafti B94, Lactobacillus plantarum HA-119, and Lactobacillus helveticus Lafti L10 for 7 weeks. It finds that probiotic supplementation modulates body weight gain, food energy efficiency, and fat accumulation caused by the HFD. This probiotic mix prevents liver damage and lipid metabolic disorders in HFD-fed obese mice. The probiotic supplementation significantly downregulates the expression of the proinflammatory cytokines interleukin-1β, tumor necrosis factor-α, and malondialdehyde (MDA) in the liver and upregulated catalase (CAT), superoxide dismutase (SOD), and nuclear respiratory factor 1 (Nrf1) expression. Mice supplemented with the probiotic mix also show different microbiota compositions, with an increase in Clostridia_UCG-014 and Lachnospiraceae_nk4a136_group and a decrease in the Dubosiella genus compared with those in mice fed only an HFD. Finally, the amounts of fecal pentanoic acid and the three bile acid species increase in mice with probiotic supplementation. Treatment with a combination of a mixture of three probiotic strains, B. lactis Lafti B94, L. plantarum HA-119, and L. helveticus Lafti L10 for 7 weeks, ameliorates the effects of HFD induced obesity in mice.

Blackcurrant Anthocyanins Attenuate Estrogen -Deficiency-Induced Bone Loss through Modulating Microbial-Derived Short-Chain Carboxylic Acids and Phytoestrogen Metabolites in Peri- and Early Postmenopausal Women.

The present study aimed to assess the effects of blackcurrant (BC) anthocyanins on concentrations of microbial-derived short-chain carboxylic acids (SCCAs) and metabolites of phytoestrogens. We then examined their associations with six-month changes in whole-body bone mineral density (BMD) and biomarkers of bone metabolism. Fecal and blood samples from a pilot randomized controlled trial were collected and analyzed from 37 eligible peri- and early postmenopausal women aged 45-60 years who were randomized into one of three treatment groups consuming one placebo capsule (control), 392 mg BC (low BC) or 784 mg BC (high BC) daily for six months. Significant differences were observed between groups at baseline in acetic, propionic, valeric, caproic and heptanoic acids (p < 0.05). Isobutyric acid significantly decreased from baseline (0 months) to six months in the control group (p < 0.05) and the high BC group had a significantly greater concentration than the control group at six months (p < 0.05). Butyric acid was significantly greater in the high BC group than low BC at six months (p < 0.05). Six-month changes in caproic and isobutyric acids showed weak correlations with changes in whole-body BMD (r = 0.3519, p < 0.05 and r = 0.3465, p < 0.05, respectively). Isovaleric and valeric acids displayed weak correlations with BALP (r = 0.3361, p < 0.05) and OPG (r = 0.3593, p < 0.05), respectively. Enterodiol was positively correlated with BALP (r = 0.6056, p < 0.01) while enterolactone was positively correlated with osteocalcin (r = 0.5902, p < 0.001) and negatively correlated with sclerostin (r = -0.3485, p < 0.05). The results suggest that BC may be a potential dietary agent to reduce postmenopausal bone loss through modulating microbially-derived SCCAs and phytoestrogen metabolites.

Lacticaseibacillus paracasei 207-27 alters the microbiota-gut-brain axis to improve wearable device-measured sleep duration in healthy adults: a randomized, double-blind, placebo-controlled trial.

Objective: Probiotics have been reported to exert beneficial effects on sleep through the gut-brain axis. Therefore, this randomized, double-blind, placebo-controlled trial assessed the effects of Lacticaseibacillus paracasei 207-27 supplementation on sleep quality and its safety and potential mechanisms. Method and study design: Healthy adults under mild stress aged 18-35 years consumed low or high doses of L. paracasei 207-27 or a placebo for 28 days. Fecal samples, blood samples, and questionnaires were collected at the baseline and the end of the intervention. Sleep quality was measured using wearable devices and Pittsburgh sleep quality index (PSQI) questionnaire. Serum inflammatory markers, corticotropin-releasing hormone, adrenocorticotropic hormone (ACTH), cortisol (COR), γ-aminobutyric acid, and 5-hydroxytryptamine levels were detected using enzyme-linked immunosorbent assay. The gut microbiota was analyzed using 16S rRNA sequencing and bioinformatics. Short-chain fatty acids levels were detected using gas chromatography-mass spectrometry. Results: Both the low-dose and high-dose groups exhibited significant improvements in wearable device- measured sleep duration compared to the placebo group. The global scores of PSQI in three groups significantly decreased after intervention without statistical difference between groups. At the phylum level, the low-dose group exhibited a higher relative abundance of Bacteroidota and a lower Firmicutes-to-Bacteroidetes (F/B) ratio. At the genus level, two treatment groups had higher relative abundance of Bacteroides and Megamonas, alongside lower levels of Escherichia-Shigella. Furthermore, the low-dose group exhibited significant increases in acetic acid, propionic acid, butyric acid, and valeric acid levels, while two treatment groups exhibited a significant decrease in COR levels. Correlation analysis revealed that the increased levels of acetic acid and butyric acid in the low-dose group may be associated with decreased ACTH. Conclusion: L. paracasei 207-27 administration in healthy adults resulted in improvements in gut microbiota community and sleep duration. The mechanisms might involve modulation of the gut microbiota structure to regulate the function of the gut-brain axis, including increases in SCFA levels and decreases in hypothalamic-pituitary-adrenal axis activity. The Chinese clinical trial registry number is ChiCTR2300069453 (https://www.chictr.org.cn/showproj.html?proj=191193, registered 16 May 2023 - retrospectively registered).

The effect of increasing canola oil and soybean oil addition to beef cattle rations based on corn silage and barley grain on the in vitro ruminal gas production and rumen fermentation

AbstractThe purpose of the current experiment was to determine the effects of ruminal fermentation parameters of the additions of canola or soybean oils at different rates (4, 8 and 12%) to beef cattle total mix rations (TMR), based on corn silage and barley grain. The addition of 4% soybean oil to TMR positively affected in vitro gas production, net energy lactation (NEL), metabolic energy (ME), and organic matter digestion (OMd). The additions of 8% and 12% of soybean oil to TMR linearly decreased ME, NEL and OMd (p &lt; 0.05). The additions of 4, 8 and 12% canola oil to the TMR linearly decreased the in vitro gas production and estimated fermentation values (ME, NEL and OMd) (p &lt; 0.05). All doses of soybean or canola oils in TMR reduced the molarities of total short‐chain fatty acids (tSFCA), acetic (AA), butyric (BA), propionic (PA), valeric (VA), iso‐valeric (IVA) and iso‐butyric acids (IBA) for in vitro fermentation fluid (p &lt; 0.05). There was a negative correlation between the increasing dietary stearic, oleic and linoleic acid and the end‐products of in vitro rumen fermentation. However, increasing dietary α‐linolenic acids had no adverse effect on in vitro ruminal fermentation end‐products. As a result, 4% addition of the soybean oil, which included a higher rate of α‐linolenic acid and saturated fatty acids and a lower rate of oleic, linoleic acids according to those of canola oil, to the TMR positively affected in vitro ruminal fermentation. In addition, the ≥8% addition of canola or soybean oil adversely affected the in vitro fermentation values.

B-172 Correlation of Microbiome Sequencing Data and Quantified Short-Chain Fatty Acids by LC-MS/MS in IBD and Non-IBD Stool Samples

Abstract Background SCFAs are the primary metabolites produced by bacterial fermentation of dietary fiber and undigested proteins. They play a crucial role in various metabolic pathways, such as regulating the host’s energy balance and anti-inflammatory processes. The most studied SCFAs are acetic acid, propionic acid and butyric acid, with an approximate molecular ratio of 60:20:20 in healthy adults. A significantly different distribution may indicate a bacterial dysbiosis. While most SCFAs have a positive impact on the host’s health, the impact of branched short-chain fatty acids (bSCFAs), such as isobutyric acid and isovaleric acid, are less well-known. In order to evaluate whether the determination of a broader SCFA panel holds additional diagnostic value, we have developed a sensitive and robust LC-MS/MS method to determine 11 C2 - C7 SCFAs in human fecal samples. Methods The LC-MS/MS method includes acetic acid (AA), propionic acid (PA), butyric acid (BA), valeric acid (VA), caproic acid (CA) and heptanoic acid (HA), as well as the isomers isobutyric acid (iBA), 2-methylbutyric acid (2-MBA), isovaleric acid (iVA), isocaproic acid (iCA) and 2-methylhexanoic acid (2-MHA). After suspending the stool samples in a stabilizing buffer, the tubes were centrifuged and 25 µl of the supernatant was mixed with an internal standard solution (10 isotopically labeled internal standards) and subsequently derivatized. After one hour, the reaction was quenched and samples were injected into an ACQUITY UPLC H-Class (Waters) with an injection cycle of 9.5 min. Analytes were measured in positive mode by ESI-MS/MS on a Xevo TQ-MS (Waters). For quantification, six calibrators and three controls covering the anticipated physiological ranges were used. Results Microbiome sequencing data identified a total of 193 species, most of which belong to the Firmicutes phylum. Next, Actinobacteria and Proteobacteria are in descending order of abundance. In our IBD samples, we see a significant dysbiosis of these ratios and orders in comparison to the screening patients. E.g. in one sample, no Bacteroidetes were found, but a high amount of Actinobacteria (40 %) were sequenced. Corresponding SCFA data detected an AA:PA:BA ratio of 76:11:10, as well as no VA, iCA, CA, 2-MHA and HA, whereas SCFA data from most screening patients showed an AA:PA:BA ratio of 60:20:20 (± 10:10:10). Conclusions After a fast and simple sample preparation and derivatization, the LC MS/MS method allows robust and sensitive measurement of all presented SCFAs from human feces samples. The preliminary analysis of the combined microbiome and SCFA data showed that the detected AA:PA:BA ratio difference could be a valid indicator for a dysbiosis or an altered microbiome, corroborating data from previous studies. While we could detect differences on bSCFAs and longer SCFAs between IBD and non-IBD patient samples in this pilot study, larger patient and control cohorts are needed in order to substantiate our initial promising findings and finally allow a robust evaluation of these parameters as diagnostic tool to monitor and determine the state of the patient microbiome.

Impact of Gut Microbiota and SCFAs in the Pathogenesis of PCOS and the Effect of Metformin Therapy.

Polycystic ovary syndrome (PCOS) is a complex disorder that impacts both the endocrine and metabolic systems, often resulting in infertility, obesity, insulin resistance, and cardiovascular complications. The aim of this study is to investigate the role of intestinal flora and its metabolites, particularly short-chain fatty acids (SCFAs), in the development of PCOS, and to assess the effects of metformin therapy on these components. SCFA levels in fecal and blood samples from women with PCOS (n=69) and healthy controls (n=18) were analyzed using Gas Chromatography-Mass Spectrometry (GC/MS) for precise measurement. Fecal microbiota were quantitatively detected by real-time polymerase chain reaction (PCR). To assess the efficacy of six months of metformin treatment, changes in the microbiota and SCFAs in the PCOS group (n=69) were also evaluated. The results revealed that women with PCOS exhibited a significant reduction in beneficial bacteria (namely, the C. leptum group and Prevotella spp.) alongside a notable overgrowth of opportunistic microorganisms (C. perfringens, C. difficile, Staphylococcus spp., and Streptococcus spp.). An overproduction of acetic acid (AA, FC=0.47, p<0.05) and valeric acid (VA, FC=0.54, p<0.05) suggests a link between elevated SCFAs and the development of obesity and PCOS. Interestingly, AA in the bloodstream might offer a protective effect against PCOS by ameliorating key symptoms such as high body mass index (r=-0.33, p=0.02), insulin resistance (r=-0.39, p=0.02), and chronic inflammation. Although serum SCFA levels showed non-significant changes following metformin treatment (p>0.05), the normalization of AA in the gut underscores that metformin exerts a more pronounced effect locally within the gastrointestinal tract. Furthermore, the study identified the most effective model for predicting the success of metformin therapy, based on serum concentrations of butyric acid (BA) and VA, achieving a 91% accuracy rate, 100% sensitivity, and 80% specificity. These promising findings highlight the potential for developing targeted interventions and personalized treatments, ultimately improving clinical outcomes for women with PCOS.

Molecular Targets of Valeric Acid: A Bioactive Natural Product for Endocrine, Metabolic, and Immunological Disorders.

Postbiotics produced by gut microbiota have exhibited diverse pharmacological activities. Valeric acid, a postbiotic material produced by gut microbiota and some plant species like valerian, has been explored to have diverse pharmacological activities. This narrative review aims to summarise the beneficial role of valeric acid for different health conditions along with its underlying mechanism. In order to get ample scientific evidence, various databases like Science Direct, PubMed, Scopus, Google Scholar and Google were exhaustively explored to collect relevant information. Collected data were arranged and analyzed to reach meaningful a conclusion regarding the bioactivity profiling of valeric acid, its mechanism, and future prospects. Valeric acid belongs to short-chain fatty acids (SCFAs) compounds like acetate, propionate, butyrate, pentanoic (valeric) acid, and hexanoic (caproic) acid. Valeric acid has been identified as one of the potent histone deacetylase (HDAC) inhibitors. In different preclinical in -vitro and in-vivo studies, valeric acid has been found to have anti-cancer, anti-diabetic, antihypertensive, anti-inflammatory, and immunomodulatory activity and affects molecular pathways of different diseases like Alzheimer's, Parkinson's, and epilepsy. These findings highlight the role of valeric acid as a potential novel therapeutic agent for endocrine, metabolic and immunity-related health conditions, and it must be tested under clinical conditions to develop as a promising drug.

The nanocellulose fiber scaffold to construct a hierarchical phenolic coating on cotton fiber surfaces for inactivating pathogens through an enhanced protein adsorption mechanism

Emerging pathogens present a significant societal threat, and biological protection textiles are expected to play a pivotal role in controlling their spread. However, incorporating highly effective pathogen transmission-blocking abilities into textiles while ensuring their large-scale production remains challenging. This work has successfully developed a hierarchically structured coating for cotton fibers, which exhibits enhanced antiviral and antibacterial functionalities compared to existing phenolic coating methods. The multilevel coating consisted of a cellulose nanofibers (CNFs) scaffold on cotton fibers, along with a phenolic layer constructed of 4,4-bis(4-hydroxyphenyl)valeric acid (DPA) on the CNF surfaces. The bioactive textile exhibited remarkable antiviral and antibacterial capabilities with exceptional durability, while demonstrating strong protein affinity for pathogen destruction. Especially, the CNFs with diameters below 10 nm show significant size effect in capturing phi6. This is primarily due to their complementary shape matching the spike proteins, resulting in an increased number of binding sites and improved inactivation effectiveness. Moreover, the modification process was demonstrated to be scalable in a pad-dry-cure line commonly employed by textile finishing factories, and the resultant coating ensured reliable safety for human skin without sacrificing wearing comfort. This approach opens up new possibilities for developing protective textiles that effectively block pathogen transmission.

Recovery and fractionation of volatile fatty acids from fermented solutions by electrodialysis: electrochemical characterization of anion-exchange membranes

Electrodialysis can be used to recover charged precursors, such as volatile fatty acids (VFAs), of the biopolymers polyhydroxyalkanoates (PHAs). In general, all VFAs are recovered in a receiver solution, despite their advantageous partial fractionation. Herein, the separation of acetic, propionic, butyric, and valeric acids by electrodialysis was evaluated using three anion-exchange membranes (namely, Ralex AMH-PES, Fumasep FAS-PET-130 and PC200D) applying cell voltages from 0V to 2.88V. The mass transfer mechanisms were evaluated by linear sweep voltammetry and chronopotentiometry. Fumasep showed a slightly greater VFAs fractionation capacity than Ralex, while it was much greater for PC200D due to the presence of tertiary amines in its fixed functional groups. Overall, increasing the operating voltage and/or time reduced the degree of VFAs fractionation with all membranes. The higher percent extraction values and greater VFAs fractionation degrees obtained with the PC200D membrane could enhance PHAs storage efficiency.