Search Results (21)

This study employs a machine learning approach to identify a small-molecule-based signature capable of predicting Alzheimer’s disease (AD). Utilizing metabolomics data from the plasma of a well-characterized cohort of 94 AD patients and 62 healthy controls; metabolite levels were assessed using the Biocrates MxP^® Quant 500 platform. Data preprocessing involved removing low-quality samples, selecting relevant biochemical groups, and normalizing metabolite data based on demographic variables such as age, sex, and fasting time. Linear regression models were used to identify concomitant parameters that consisted of the data for a given metabolite within each of the biochemical families that were considered. Detection of these “concomitant” metabolites facilitates normalization and allows sample comparison. Residual analysis revealed distinct metabolite profiles between AD patients and controls across groups, such as amino acid-related compounds, bile acids, biogenic amines, indoles, carboxylic acids, and fatty acids. Correlation heatmaps illustrated significant interdependencies, highlighting specific molecules like carnosine, 5-aminovaleric acid (5-AVA), cholic acid (CA), and indoxyl sulfate (Ind-SO₄) as promising indicators. Linear Discriminant Analysis (LDA), validated using Leave-One-Out Cross-Validation, demonstrated that combinations of four or five molecules could classify AD with accuracy exceeding 75%, sensitivity up to 80%, and specificity around 79%. Notably, optimal combinations integrated metabolites with both a tendency to increase and a tendency to decrease in AD. A multivariate strategy consistently identified included 5-AVA, carnosine, CA, and hypoxanthine as having predictive potential. Overall, this study supports the utility of combining data of plasma small molecules as predictors for AD, offering a novel diagnostic tool and paving the way for advancements in personalized medicine. Full article

A new green water treatment agent, a poly(aspartic acid)-modified polymer (PASP/5–AVA), was synthesized using polysuccinimide and 5-aminovaleric acid (5-AVA) in a hybrid system. The structure was characterized, and the scale and corrosion inhibition performance were carried out with standard static scale inhibition and electrochemical methods, respectively. The mechanism was explored using XRD, XPS, SEM, and quantum chemistry calculations. The results indicated that PASP/5–AVA exhibited better scale and corrosion inhibition performance than PASP and maintained efficacy and thermal stability of the scale inhibition effect for a long time. Mechanistic studies indicated that PASP/5–AVA interferes with the normal generation of CaCO₃ and CaSO₄ scales through lattice distortion and dispersion, respectively; the combined effect of an alkaline environment and terminal electron-withdrawing -COOH groups can induce the stable C^- ionic state formation in -CH₂- of the extended side chain, thus enhancing its chelating ability for Ca²⁺ ions. At the same time, the extension of the side chain length also enhances the adsorption ability of the agent on the metal surface, forming a thick film and delaying the corrosion of the metal surface. This study provides the necessary theoretical reference for the design of green scale and corrosion agents. Full article

Per- and poly-fluoroalkyl substances (PFAS) exhibit high persistence in the environment and accumulate within the human body, warranting a thorough assessment of their toxicity. In this study, we exposed mice (male C57BL/6J mice aged 8 weeks) to a composite of nine PFAS, encompassing both long-chain PFAS (e.g., perfluorooctanoic acid and perfluorooctanesulfonic acid) and short-chain PFAS (e.g., perfluorobutanoic acid and perfluorobutanesulfonic acid). The exposure concentrations of PFAS were equivalent to the estimated daily human intake in the composition reported (1 µg/L (sum of the nine compounds), representing the maximum reported exposure concentration). Histological examination revealed hepatocyte vacuolization and irregular hepatocyte cord arrangement, indicating that exposure to low levels of the PFAS mixture causes morphological changes in liver tissues. Transcriptome analysis revealed that PFAS exposure mainly altered a group of genes related to metabolism and chemical carcinogenesis. Machine learning analysis of the liver metabolome showed a typical concentration-independent alteration upon PFAS exposure, with the annotation of substances such as glutathione and 5-aminovaleric acid. This study demonstrates that daily exposure to PFAS leads to morphological changes in liver tissues and alters the expression of metabolism- and cancer-related genes as well as phospholipid metabolism. Full article

Pseudomonas putida strain U can be grown using, as sole carbon sources, the biogenic amines putrescine or cadaverine, as well as their catabolic intermediates, ɣ-aminobutyrate or δ-aminovalerate, respectively. Several paralogs for the genes that encode some of the activities involved in the catabolism of these compounds, such as a putrescine-pyruvate aminotransferase (spuC1 and spuC2 genes) and a ɣ-aminobutyrate aminotransferase (gabT1 and gabT2 genes) have been identified in this bacterium. When the expression pattern of these genes is analyzed by qPCR, it is drastically conditioned by supplying the carbon sources. Thus, spuC1 is upregulated by putrescine, whereas spuC2 seems to be exclusively induced by cadaverine. However, gabT1 increases its expression in response to different polyamines or aminated catabolic derivatives from them (i.e., ɣ-aminobutyrate or δ-aminovalerate), although gabT2 does not change its expression level concerning no-amine unrelated carbon sources (citrate). These results reveal differences between the mechanisms proposed for polyamine catabolism in P. aeruginosa and Escherichia coli concerning P. putida strain U, as well as allow a deeper understanding of the enzymatic systems used by this last strain during polyamine metabolism. Full article

Amino acids are involved in various chemical reactions in vivo, and changes in several amino acids in urine are related to certain disease states. Therefore, developing an efficient method to analyze the amino acids in urine is useful in the timely diagnosis of diseases. In this study, we developed a high-performance liquid chromatography (HPLC) fluorescence method for the quantitative analysis of urinary amino acids using the fluorescence derivatization reagent 2,3-naphthalenedicarboxaldehyde (NDA). NDA was selected because it does not require heating for the reaction and can react within a short time, rendering its use in clinical settings feasible. The reaction temperature, reaction time, and other derivatization conditions were optimized, and the reaction was found to be completed in 5 min at 25 °C. The separation of NDA–amino acids was investigated on an octadecylsilyl (ODS) column under gradient conditions. The mobile phase was a mixture of water–acetonitrile–trifluoroacetic acid. Eighteen NDA–amino acids (histidine (His), arginine (Arg), asparagine (Asn), glutamine (Gln), citrulline (Cit), serine (Ser), aspartic acid (Asp), threonine (Thr), glutamic acid (Glu), glycine (Gly), tyrosine (Tyr), alanine (Ala), tryptophan (Trp), valine (Val), phenylalanine (Phe), isoleucine (Ile), leucine (Leu), and 5-aminovaleric acid (internal standard)) were separated within 100 min under optimal conditions. The calibration curves showed good linearity in the range of 0.25–25 pmol per injection with correlation coefficients of >0.998. The limits of quantification for NDA–amino acids were 16.7–74.7 fmol. The developed analytical method was applied to a human urine sample and 16 amino acids (His, Arg, Asn, Gln, Cit, Ser, Thr, Glu, Gly, Tyr, Ala, Trp, Val, Phe, Ile, and Leu) were quantified. The urinary amino acid concentrations were 5–960 μM. Urinary amino acid analysis using this method is expected to be clinically applicable as a novel biomarker for diseases affecting the bladder, urinary tract, and kidneys. Full article

Acute stress response triggers various physiological responses such as energy mobilization to meet metabolic demands. However, the underlying molecular changes in the brain remain largely obscure. Here, we used a brief water avoidance stress (WAS) to elicit an acute stress response in mice. By employing RNA-sequencing and metabolomics profiling, we investigated the acute stress-induced molecular changes in the mouse whole brain. The aberrant expression of 60 genes was detected in the brain tissues of WAS-exposed mice. Functional analyses showed that the aberrantly expressed genes were enriched in various processes such as superoxide metabolism. In our global metabolomic profiling, a total of 43 brain metabolites were significantly altered by acute WAS. Metabolic pathways upregulated from WAS-exposed brain tissues relative to control samples included lipolysis, eicosanoid biosynthesis, and endocannabinoid synthesis. Acute WAS also elevated the levels of branched-chain amino acids, 5-aminovalerates, 4-hydroxy-nonenal-glutathione as well as mannose, suggesting complex metabolic changes in the brain. The observed molecular events in the present study provide a valuable resource that can help us better understand how acute psychological stress impacts neural functions. Full article

Cystinosis is a rare, devastating hereditary disease secondary to recessive CTNS gene mutations. The most commonly used diagnostic method is confirmation of an elevated leukocyte cystine level; however, this method is expensive and difficult to perform. This study aimed to identify candidate biomarkers for the diagnosis and follow-up of cystinosis based on multiomics studies. The study included three groups: newly-diagnosed cystinosis patients (patient group, n = 14); cystinosis patients under treatment (treatment group, n = 19); and healthy controls (control group, n = 30). Plasma metabolomics analysis identified 10 metabolites as candidate biomarkers that differed between the patient and control groups [L-serine, taurine, lyxose, 4-trimethylammoniobutanoic acid, orotic acid, glutathione, PE(O-18:1(9Z)/0:0), 2-hydroxyphenyl acetic acid, acetyl-N-formil-5-metoxikinuramine, 3-indoxyl sulphate]. As compared to the healthy control group, in the treatment group, hypotaurine, phosphatidylethanolamine, N-acetyl-d-mannosamine, 3-indolacetic acid, p-cresol, phenylethylamine, 5-aminovaleric acid, glycine, creatinine, and saccharic acid levels were significantly higher, and the metabolites quinic acid, capric acid, lenticin, xanthotoxin, glucose-6-phosphate, taurine, uric acid, glyceric acid, alpha-D-glucosamine phosphate, and serine levels were significantly lower. Urinary metabolomic analysis clearly differentiated the patient group from the control group by means of higher allo-inositol, talose, glucose, 2-hydroxybutiric acid, cystine, pyruvic acid, valine, and phenylalanine levels, and lower metabolite (N-acetyl-L-glutamic acid, 3-aminopropionitrile, ribitol, hydroquinone, glucuronic acid, 3-phosphoglycerate, xanthine, creatinine, and 5-aminovaleric acid) levels in the patient group. Urine metabolites were also found to be significantly different in the treatment group than in the control group. Thus, this study identified candidate biomarkers that could be used for the diagnosis and follow-up of cystinosis. Full article

Influenza represents a major and ongoing public health hazard. Current collaborative efforts are aimed toward creating a universal flu vaccine with the goals of both improving responses to vaccination and increasing the breadth of protection against multiple strains and clades from a single vaccine. As an intermediate step toward these goals, the current work is focused on evaluating the systemic host response to vaccination in both normal and high-risk populations, such as the obese and geriatric populations, which have been linked to poor responses to vaccination. We therefore employed a metabolomics approach using a time-course (n = 5 time points) of the response to human vaccination against influenza from the time before vaccination (pre) to 90 days following vaccination. We analyzed the urinary profiles of a cohort of subjects (n = 179) designed to evenly sample across age, sex, BMI, and other demographic factors, stratifying their responses to vaccination as “High”, “Low”, or “None” based on the seroconversion measured by hemagglutination inhibition assay (HAI) from plasma samples at day 28 post-vaccination. Overall, we putatively identified 15,903 distinct, named, small-molecule structures (4473 at 10% FDR) among the 895 samples analyzed, with the aim of identifying metabolite correlates of the vaccine response, as well as prognostic and diagnostic markers from the periods before and after vaccination, respectively. Notably, we found that the metabolic profiles could unbiasedly separate the high-risk High-responders from the high-risk None-responders (obese/geriatric) within 3 days post-vaccination. The purine metabolites Guanine and Hypoxanthine were negatively associated with high seroconversion (p = 0.0032, p < 0.0001, respectively), while Acetyl-Leucine and 5-Aminovaleric acid were positively associated. Further changes in Cystine, Glutamic acid, Kynurenine and other metabolites implicated early oxidative stress (3 days) after vaccination as a hallmark of the High-responders. Ongoing efforts are aimed toward validating these putative markers using a ferret model of influenza infection, as well as an independent cohort of human seasonal vaccination and human challenge studies with live virus. Full article

Fermentation has been considered as an effective means to improve the feed nutrient digestibility of corn stalks, and it is beneficial to animal growth performance and health. The beneficial functions of fermented corn stalks are related to the variety of metabolites produced through fermentation, but the nature of these components is still unclear. In this study, gas chromatography–mass spectrometry, combined with principal component analysis and partial least squares discriminant analysis, was used to explore the differential metabolites of corn stalks before and after Aspergillus niger fermentation. A total of 32 potential characteristic compounds were obtained, mainly including sugar and glycoside derivatives, organic acids and their derivatives, alcohol compounds, benzene and its substituted derivatives, amino acids, phenolic compounds, and flavonoids. Compared with the metabolites in corn straw before fermentation, the relative content of D-threitol, mannitol-1-phosphate, coniferin, citrazinic, oxoglutaric acid, chenodeoxycholic acid, naproxen, 5-aminovaleric acid, vanillin, catechin, and UDP-glucuronic acid was significantly increased, and the relative content of N-acetylgalactosamine, heneicosanoic acid, chlorogenic acid, and adenosine was significantly decreased. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that 20 metabolic pathways corresponded to the differential characteristic metabolites. The results of this study will provide theoretical support for the quality evaluation of fermented corn stalks and high-value product development in the future. Full article

Early detection of oral candidiasis is essential. However, most currently available methods are time-consuming and useful only for screening patients. Previous studies on the relationship between oral candidiasis and saliva have focused on saliva volume and not on its components. Therefore, to clarify the effects of oral candidiasis on salivary metabolites, the relationship between salivary components and oral candidiasis was investigated by comparing the salivary metabolites of oral candidiasis patients and those not previously diagnosed with candidiasis. Forty-five participants visiting our university hospital were included and classified into two groups, the Candida group and the control group, based on the Candida detection test results. The unstimulated saliva was collected using the spitting method over 15 min, and the stimulated saliva was collected using the gum-chewing method over 10 min. The saliva volume was measured, and the saliva samples were frozen and analyzed metabolomically. Metabolome analysis revealed 51 metabolites with peak detection rates exceeding 50%. There was no significant difference in age and sex between the Candida and control groups. In the Candida group, five metabolites (tyrosine, choline, phosphoenolpyruvate, histidine, and 6-phosphogluconate) were significantly elevated in the unstimulated, two (octanoic acid and uridine monophosphate(UMP)) were significantly increased, and four (ornithine, butyrate, aminovalerate and aminolevulinate) were significantly decreased in the stimulated saliva. This study suggests the possibility of identifying metabolites specific to patients with oral candidiasis, which could aid prompt diagnosis. Full article

Recent studies have shown promise for the use of probiotics in modulating behaviour through the microbiota–gut–brain axis. In the present study, we assessed the impact of two probiotic strains in mitigating autism-related symptomology in the BTBR T⁺ Itpr3^tf/J mouse model of autism spectrum disorder (ASD). Male juvenile BTBR mice were randomized into: (1) control, (2) Lr probiotic (1 × 10⁹ CFU/mL Lacticaseibacillus rhamnosus HA-114), and (3) Ls probiotic groups (1 × 10⁹ CFU/mL Ligilactobacillus salivarius HA-118) (n = 18–21/group), receiving treatments in drinking water for 4 weeks. Gut microbiota profiling by 16S rRNA showed Lr, but not Ls supplementation, to increase microbial richness and phylogenetic diversity, with a rise in potential anti-inflammatory and butyrate-producing taxa. Assessing serum and brain metabolites, Lr and Ls supplementation produced distinct metabolic profiles, with Lr treatment elevating concentrations of potentially beneficial neuroactive compounds, such as 5-aminovaleric acid and choline. As mitochondrial dysfunction is often observed in ASD, we assessed mitochondrial oxygen consumption rates in the prefrontal cortex and hippocampus. No differences were observed for either treatment. Both Lr and Ls treatment reduced behavioural deficits in social novelty preference. However, no changes in hyperactivity, repetitive behaviour, and sociability were observed. Results show Lr to impart positive changes along the microbiota–gut–brain axis, exhibiting beneficial effects on selected behaviour, gut microbial diversity, and metabolism in BTBR mice. Full article

Cross-talk between the immune system and the brain is essential to neuronal development, neuronal excitability, neuroplasticity, and neurotransmission. Gut microbiota are essential to immune system development and immune function; hence, it is essential to consider more broadly the microbiota-immune-brain axis in neurodevelopment. The gut, brain, and microbial metabolomes obtained from C57Bl/6 and T-cell-deficient mice across four developmental timepoints (postnatal day 17, 24, 28, and 84) were studied by ¹H NMR spectroscopy. 16S rRNA gene sequencing was performed on cecal and fecal samples. In the absence of T-cells, the developmental trajectory of the gut microbiota and of the host’s metabolic profile was altered. The novel insights from this work include (1) the requirement of functional T-cells for the normal trajectory of microbiotal development and the metabolic maturation of the supra-organism, (2) the potential role for Muribaculaceae taxa in modulating the cecal availability of metabolites previously implicated with a role in the gut-brain axis in T-cell deficient mice, and (3) the impact of T-cell-deficiency on central levels of neuroactive metabolites. Full article

(1) Background: Human milk oligosaccharides (HMOs) may support immune protection, partly via their action on the early-life gut microbiota. Exploratory findings of a randomized placebo-controlled trial associated 2′fucosyllactose (2′FL) and lacto-N-neotetraose (LNnT) formula feeding with reduced risk for reported bronchitis and lower respiratory tract illnesses (LRTI), as well as changes in gut microbiota composition. We sought to identify putative gut microbial mechanisms linked with these clinical observations. (2) Methods: We used stool microbiota composition, metabolites including organic acids and gut health markers in several machine-learning-based classification tools related prospectively to experiencing reported bronchitis or LRTI, as compared to no reported respiratory illness. We performed preclinical epithelial barrier function modelling to add mechanistic insight to these clinical observations. (3) Results: Among the main features discriminant for infants who did not experience any reported bronchitis (n = 80/106) or LRTI (n = 70/103) were the 2-HMO formula containing 2′FL and LNnT, higher acetate, fucosylated glycans and Bifidobacterium, as well as lower succinate, butyrate, propionate and 5-aminovalerate, along with Carnobacteriaceae members and Escherichia. Acetate correlated with several Bifidobacterium species. By univariate analysis, infants experiencing no bronchitis or LRTI, compared with those who did, showed higher acetate (p < 0.007) and B. longum subsp. infantis (p ≤ 0.03). In vitro experiments demonstrate that 2′FL, LNnT and lacto-N-tetraose (LNT) stimulated B. longum subsp. infantis (ATCC15697) metabolic activity. Metabolites in spent culture media, primarily due to acetate, supported epithelial barrier protection. (4) Conclusions: An early-life gut ecology characterized by Bifidobacterium-species-driven metabolic changes partly explains the observed clinical outcomes of reduced risk for bronchitis and LRTI in infants fed a formula with HMOs. (Trial registry number NCT01715246.). Full article

Halitosis is mainly caused by the action of oral microbes. The purpose of this study was to investigate the differences in salivary microbes and metabolites between subjects with and without halitosis. Of the 52 participants, 22 were classified into the halitosis group by the volatile sulfur compound analysis on breath samples. The 16S rRNA gene amplicon sequencing and metabolomics approaches were used to investigate the difference in microbes and metabolites in saliva of the control and halitosis groups. The profiles of microbiota and metabolites were relatively different between the halitosis and control groups. The relative abundances of Prevotella, Alloprevotella, and Megasphaera were significantly higher in the halitosis group. In contrast, the relative abundances of Streptococcus, Rothia, and Haemophilus were considerably higher in the control group. The levels of 5-aminovaleric acid and n-acetylornithine were significantly higher in the halitosis group. The correlation between identified metabolites and microbiota reveals that Alloprevotella and Prevotella might be related to the cadaverine and putrescine pathways that cause halitosis. This study could provide insight into the mechanisms of halitosis. Full article

Integrative multiomics data analysis provides a unique opportunity for the mechanistic understanding of colorectal cancer (CRC) in addition to the identification of potential novel therapeutic targets. In this study, we used public omics data sets to investigate potential associations between microbiome, metabolome, bulk transcriptomics and single cell RNA sequencing datasets. We identified multiple potential interactions, for example 5-aminovalerate interacting with Adlercreutzia; cholesteryl ester interacting with bacterial genera Staphylococcus, Blautia and Roseburia. Using public single cell and bulk RNA sequencing, we identified 17 overlapping genes involved in epithelial cell pathways, with particular significance of the oxidative phosphorylation pathway and the ACAT1 gene that indirectly regulates the esterification of cholesterol. These findings demonstrate that the integration of multiomics data sets from diverse populations can help us in untangling the colorectal cancer pathogenesis as well as postulate the disease pathology mechanisms and therapeutic targets. Full article