PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “plasma metabolites”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2025

Plasma metabolites mediate the causal relationship between gut microbiota and erectile dysfunction: insights from Mendelian randomization study.

BACKGROUND: While the relationship between gut microbiota and erectile dysfunction (ED) has been reported, the specific pathways involved remain unclear. AIM: This study aims to investigate the causal relationship between gut microbiota and ED, and to identify the potential role of plasma metabolites as mediators. METHODS: Utilizing aggregated genome-wide association study (GWAS) data, a comprehensive two-sample Mendelian randomization (MR) analysis was performed involving 196 gut microbiota taxa, 1400 plasma metabolites and ED. Causal relationships between gut microbiota, plasma metabolites and ED were explored. In addition, mediation analysis was applied to identify the pathway from gut microbiota to ED mediated by plasma metabolites. OUTCOMES: This study reveals that plasma metabolites act as mediators regulating the influence of gut microbiota on ED. RESULTS: MR analysis identified causal relationships between six gut microbial taxa and ED, with Butyrivibrio increasing the risk of ED, while Alistipes, Prevotella 9, Dialister, Marvinbryantia, and LachnospiraceaeUCG010 exhibited protective effects. Additionally, 45 plasma metabolites demonstrated causal associations with ED. Finally, mediation analysis revealed four mediation relationships. Sensitivity analysis indicated no heterogeneity or pleiotropy in this study. CLINICAL IMPLICATIONS: Modulating gut microbiota or targeting specific metabolites may offer new therapeutic approaches for ED, highlighting the potential for microbiome-based interventions. STRENGTHS AND LIMITATIONS: The MR approach and large-scale GWAS data provide robust causal evidence, but the findings are limited by their focus on European populations and lack of experimental validation. Further studies are needed to confirm these mechanisms in diverse cohorts and functional models. CONCLUSION: This study establishes a causal link between gut microbiota, plasma metabolites, and ED, identifying specific microbial taxa and metabolites as key contributors to ED risk. The mediating role of plasma metabolites highlights potential therapeutic strategies, such as probiotics or dietary interventions targeting harmful metabolites.

Mendelian randomization↗
PubMed2025

Exploring the causal role of plasma metabolites in pediatric asthma: a Mendelian randomization study.

BACKGROUND: Pediatric asthma (PA) is the prevailing chronic respiratory ailment in childhood. A better understanding of plasma metabolites is the goal for elucidating the molecular pathological mechanisms of PA and investigating novel therapeutic approaches. METHODS: Data for PA from Genome-Wide Association Studies (GWAS) was derived from the IEU-OpenGWAS project, featuring a collection of 1400 plasma metabolites. The inverse-variance weighting (IVW) method assessed causal relationships between plasma metabolites and PA, with measures taken to mitigate horizontal pleiotropy and heterogeneity. To select instrumental variables, a genome-wide significance threshold (p&#x2009;<&#x2009;5&#x2009;&#xd7;&#x2009;10-8) was applied to ensure robust genetic instruments. A Bonferroni correction controlled for multiple testing, with statistical significance defined as p&#x2009;<&#x2009;3.57&#x2009;&#xd7;&#x2009;10-5) (0.05/1400). To further substantiate outcomes, a reverse Mendelian randomization analysis was conducted. RESULTS: Research found 91 plasma metabolites linked to PA, ten of which showed significant associations. Of note, 20:4n6 levels (IVW: OR (95% CI) = 1.062 (1.030 to 1.094) and G/C16 (IVW: OR (95% CI) = 0.886 (0.832 to 0.943) were identified as pivotal exposure factors for PA. CONCLUSIONS: This study highlights 10 plasma metabolites that may have significant associations with PA incidence, with 20:4n6 levels and G/C16 potentially serving as valuable biomarkers for the early detection and management of PA.

Humans↗
PubMed2026

Inflammatory cytokines mediate thoracic aortic aneurysm formation via plasma metabolites: A two-step Mendelian randomization and single cell sequencing-based investigation.

Thoracic aortic aneurysm (TAA) is a life-threatening condition characterized by pathological dilation of the aorta. While inflammatory responses have been implicated in TAA pathogenesis, the causal relationships remain elusive. This study aimed to elucidate potential causal associations between inflammatory cytokines, plasma metabolites, and TAA risk using Mendelian randomization (MR) analysis. We conducted bidirectional two-sample MR analysis utilizing genome-wide association study data from 91 inflammatory cytokines (n&#x2005;=&#x2005;14,824), 1400 plasma metabolites (n&#x2005;=&#x2005;8299), and TAA (n&#x2005;=&#x2005;385,857). The inverse-variance weighted method served as the primary analytical approach, with comprehensive sensitivity analyses performed to assess pleiotropy and heterogeneity. Two-step MR analysis was employed to explore potential mediating roles of plasma metabolites. Single-cell sequencing analysis was utilized to detect cell type enrichment and elucidate cellular functions of identified cytokines. Additionally, we conducted an analysis to identify druggable proteins as potential therapeutic targets for TAA. MR analysis revealed that genetically-determined increases in C-X-C motif chemokine 10 (CXCL10) (odds ratios [OR]&#x2005;=&#x2005;1.149, 95% confidence interval [CI]: 1.009-1.309, P&#x2005;=&#x2005;.037) and fibroblast growth factor 5 (OR&#x2005;=&#x2005;1.101, 95% CI: 1.013-1.196, P&#x2005;=&#x2005;.024) were associated with elevated TAA risk. Conversely, C-C motif chemokine 20 (CCL20) (OR&#x2005;=&#x2005;0.870, 95% CI: 0.759-0.996, P&#x2005;=&#x2005;.043) and CD40L receptor (CD40) (OR&#x2005;=&#x2005;0.906, 95% CI: 0.827-0.992, P&#x2005;=&#x2005;.033) demonstrated inverse associations with TAA risk. Two-step MR analysis identified potential mediating metabolites: the phosphate to linoleoyl-arachidonoyl-glycerol ratio for CXCL10, thyroxine and X-24585 for FGF-5, and the creatine to carnitine ratio for CCL20. Single-cell sequencing analysis revealed enrichment of these cytokines in specific cell types and pathways relevant to TAA pathogenesis. Drug-gene interaction analysis identified CXCL10, CCL20, and CD40 as potential targets for treatment of TAA. This study provides robust genetic evidence supporting causal relationships between specific inflammatory cytokines and TAA risk, with plasma metabolites potentially mediating these effects. CXCL10 and FGF-5 were identified as potential risk factors, while CCL20 and CD40 may confer protective effects. These findings offer novel insights into TAA pathogenesis and suggest potential targets for intervention. Further research is warranted to elucidate the underlying mechanisms and validate these results across diverse populations.

Aortic Aneurysm, Thoracic↗
PubMed2026

A Mendelian Randomization Study of Immune Cell Traits and Plasma Metabolites in Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) is an autoimmune disorder of the thyroid. While immune cells are implicated in its pathogenesis, their specific roles have yet to be fully clarified. A two-sample Mendelian randomization (MR) analysis was conducted integrating genome-wide association study (GWAS) summary statistics from large public datasets for immune cell traits (ebi-a-GCST90001391 to ebi-a-GCST90002121), plasma metabolites (GCST90199621-9020102), and HT (ebi-a-GCST90018855). Causal effects were estimated using inverse-variance weighted (IVW) methods, with MR-Egger, weighted median, and leave-one-out analyses to assess pleiotropy and robustness. Bidirectional and mediation MR analyses were further applied to test directionality and identify potential metabolite-mediated pathways. CD3&#x207a;CD4&#x207a;CD25&#x207a;CD39&#x207a;Treg cells were quantified in peripheral blood samples using flow cytometry. Isovalerylcarnitine (C5) was measured by liquid chromatography tandem mass spectrometry. IVW analysis identified 32 immune cell phenotypes significantly associated with HT risk (P < 0.05 after FDR correction). Reverse MR analysis demonstrated that HT was positively causally linked with 2 immune characteristics, while 4 immune characteristics (all P < 0.05) were inversely associated with HT. Sensitivity analyses revealed no horizontal pleiotropy or heterogeneity. Additionally, the IVW method preliminarily identified 9 plasma metabolites as causally related to HT, including risk-enhancing C5 (OR = 1.120, 95% CI: 1.032-1.215, P = 0.006) and protective ergothioneine (OR = 0.958, 95% CI: 0.927-0.990, P = 0.010). Two-step MR mediation identified C5 as a candidate mediator connecting CD3&#x207a; CD39&#x207a; Treg to HT (mediation proportion 8.89%, 95% CI: 2.34%-15.4%, P = 0.008). Flow cytometry elevated CD39&#x207a;Treg levels and plasma C5 in HT patients, with C5 positively correlated with CD39&#x207a;Treg cells proportion. This study establishes novel causal links between immune cell phenotypes and HT, and highlights plasma metabolites, particularly C5, as potential mediators in HT pathogenesis. These findings deepen mechanistic understanding of autoimmune thyroid disease and may guide future biomarker and therapeutic target discovery.

Humans↗
PubMed2026

Association between the gut microbiome and plasma metabolites linked to vocalization-based temperament in Merino sheep.

BACKGROUND: Temperament, as a determinant of behavioural and emotional responses, has a substantial adaptive value in different environments. This study aims to investigate the association between the gut microbiota and temperament plasticity, and clarify the potential metabolic mechanism that underpins that association by running a multi-omics study in sheep. METHODS: The TrackSheep research cohort was generated using 200 healthy juvenile Merino ewes, and the rumen microbiota, plasma metabolome, and temperament phenotype was measured. RESULTS: Rumen metagenomic analysis identified 25 microbial species and 16 MetaCyc pathways that explained 37.5% and 11.1%, respectively, of the variation in temperament as estimated using the vocal reactivity to stress. Among these, the &#x3b3;-aminobutyric acid (GABA) shunt and allantoin degradation pathways showed the strongest associations with vocal behaviour. Multi-omic integration linked these microbial pathways to plasma metabolites that are involved in neurotransmission, antioxidant defense, and energy metabolism, including acetyl-L-carnitine (ALCAR) and urocortisone, which partially mediated the effects of microbial pathways on vocalisations. Notably, functional genomic and mediation analyses indicated that the abundance of Cryptobacteroides sp902761655 was associated with the activity of GABA shunt pathway, where GABA co-occurred with succinate production, in turn correlating with reduced inhibitory effects of ALCAR on stress-susceptible temperament. Although plasma metabolite shifts observed immediately after behavioural tests reflected stress exposure, their associations with rumen microbiota highlight microbiome-metabolite interplay that could underly behavioural variation. CONCLUSIONS: Our study provides the first large-scale multi-omics evidence linking the rumen microbiome to a dimension of emotional reactivity in livestock, while underscoring the need for longitudinal and experimental validation to establish causal mechanisms. Video Abstract.

Animals↗
PubMed1978

Interference in assays for hydralazine in humans by a major plasma metabolite, hydralazine pyruvic acid hydrazone.

The present study showed that published spectrophotometric and GLC methods for hydralazine in plasma do not distinguish between the drug and a major plasma metabolite, hydralazine pyruvic acid hydrazone. These methods involve the acid treatment of the sample, which hydrolyzes that hydrazone back to hydralazine. A specific GLC assay for the hydrazone was developed and involves its selective extraction from plasma and transformation to 3-trifluoromethyl-s-triazolo[3,4-a]phthalazine. This derivative could be sensitively measured by GLC using an electron-capture detector. With this procedure, it was shown that most "apparent hydralazine" in plasma is the hydrazone, which forms rapidly from hydralazine and endogenous pyruvic acid. Previous work indicated that the hydrazone was inactive when administered intravenously to rabbits.

Chromatography, Gas↗
PubMed1978

Stability of plasma metabolites and hormones in parturient dairy cows.

Metabolic changes that accompany the transition from parturition to lactation in dairy cows were studied. To measure these changes, plasma samples were obtained from 20 mature Holstein-Friesian dairy cows 10 days before through 10 days after parturition. They were analyzed for glucose, free fatty acids (FFA), lactic acid, ketone bodies, glucocorticoids, insulin, and growth hormone concentration. Lactic acid and glucocorticoids remained constant during the experiment, except for the day of parturition itself. In the prepartum period, changes were not detected in concentrations of hormones (glucocorticoids, insulin, and growth hormone), whereas, plasma metabolites began changing prior to parturition. Most evident were prepartum increased in FFA, ketones, and glucose. Postpartum plasma glucose concentration rapidly returned to prepartum concentrations. Plasma concentration of FFA and ketone bodies remained elevated for longer periods.

Animals↗
PubMed1979

Effect of hypothermia on plasma metabolites in preterm newborn infants with particular references to plasma free amino acids.

Blood glucose, blood lactate, plasma free fatty acids, plasma alpha-amino nitrogen, plasma free amino acids and blood urea nitrogen were measured in 15 hypothermic preterm infants (mean rectal temperature: 34.5 +/- 0.28 degrees C) during a 2-hour 'warming-up' period following admission to our neonatal intensive care unit. Hypothermia was associated with lactacidemia and hyperalaninemia. The increase in body temperature of the infants resulted in the decrease of lactacidemia and hyperalaninemia. Normal levels of other metabolites remained unchanged.

Amino Acids↗
PubMed1975

Identification of some plasma metabolites of 6, 7-3-H-estrone glucosiduronate in male dogs.

Following the constant infusion of 6, 7-3-H-estrone glucosiduronate in male dogs for a period of 120 minutes, the radioactive metabolites present in the plasma were separated by solvent partition, DEAE-Sephapadex, Celite partition and thin layer chromatography. The identities of the individual estrogens and estrogen conjugates were confirmed by specific activity determinations after chromatography in several different solvent systems, enzyme hydrolysis and steroids and their derivatives. Most of the radioactivity in the plasma was identified as estrone glucosiduronate. The major metabolite present was estradiol-17-beta-3-glucosiduronate. Small amounts of estradiol-17-alpha-3-glucosiduronate and free estrone were also identified. Three other minor conjugates were separated, but positive identification could not be made.

Animals↗
PubMed1977

Acebutolol metabolite plasma concentration during chronic oral therapy.

1 We have measured the plasma concentration of acebutolol and a major metabolite in patients on chronic oral therapy with this drug, using a new assay, specific for each species. Our study suggests: 2 The acetyl metabolite was present in concentrations greater than those of acebutolol at all times during the dosing interval in all seven subjects. 3 The ratio of the mean steady-state plasma concentrations of the acetyl metabolite to unchanged acebutolol was 2.7 +/- 1.0. 4 Previous studies using non-specific methods that measure plasma concentrations of the acetyl metabolite and acebutolol as a single species cannot be used to determine pharmacokinetic parameters or to provide reliable correlations of plasma drug concentration with effect. 5 Future studies determining plasma concentration of acebutolol should take this metabolite into account. 6 Further work will be necessary to determine the metabolite's contribution to acebutolol's effects in man.

Acebutolol↗
PubMed1978

Stability of plasma metabolites and hormones in lactating dairy cows.

Plasma concentration stability of glucose, free fatty acids, ketone bodies, growth hormone, insulin were determined in lactating dairy cows. Concentrations of these metabolites and hormones were measured during a 36- to 48-hour period in 3 normal, mature dairy cows in the 2nd month of lactation. Samples were taken at 30-minute intervals; also, intensive sampling (every 10 minutes) was done at varying times in relation to feeding and milking. Of the 5 components measured, glucose concentration was the most stable, easiest to assay, and most reliable for use as a diagnostic aid in assessing metabolic carbohydrate disturbances in dairy cattle.

Animals↗
PubMed1978

Effect of fasting on plasma metabolites and hormones in lactating dairy cows.

Metabolic and pathophysiologic changes of secondary ketosis were studied. Plasma samples were obtained from a group of 8 mature, lactating dairy cows before, during, and after a 48-hour fast. These samples were analyzed for glucose, free fatty acids (FFA), lactic acid, ketone bodies, glucocorticoids, insulin, and growth hormone concentrations. In the prefasting period, metabolites and hormones remained constant. Lactic acid and glucocorticoids also remained stable during the entire experiment, except on the 1st day after termination of the fast, when glucocorticoids increased significantly (P less than 0.05). Glucose values decreased significantly (P less than 0.01) with the onset of fasting, began to rise halfway through the fast, and were elevated following termination of the fast. Plasma glucose concentration returned to normal by the end of the experiment. Plasma FFA concentrations increased during the early portions of the fast and decreased thereafter. Plasma ketone body concentration responded similarly, but the change occurred approximately 12 hours after the plasma FFA changes. A value determined as ketotic was reached during the fast (14.6 +/- 1.3 mg/dl). Insulin concentrations remained low during the fast and increased after fasting. Plasma growth hormone concentration increased to a new plateau in response to fasting and then decreased somewhate after fasting was ended.

Animals↗
PubMed1977

Determination of the optimum dietary proportions of lysine and tryptophan for growing pigs based on growth, food intake and plasma metabolites.

Weanling crossbred pigs were divided into 24 groups and fed one of three levels of lysine and one of eight levels of tryptophan in a 3 X 8 factorial design to determine the optimum dietary proportions of these two amino acids. Weight gain and feed efficiency, and changes in plasma levels of lysine, tryptophan and urea were the response criteria. The tryptophan "requirement" and the optimum lysine:tryptophan ratio were estimated for each of the three lysine levels. The data indicate a tryptophan requirement of 0.19% to 0.23% for the 3-week-old pig when the lysine level is adequate. For pigs of this age a lysine:tryptophan ratio of from 4 to 5 was about optimum.

Age Factors↗
PubMed1977

Determination of the optimum dietary proportions of lysine and tryptophan for growing rats based on growth, food intake and plasma metabolites.

Weanling rats were divided into 24 groups and fed one of three levels of lysine and one of eight levels of tryptophan in a 3 X 8 factorial design to determine the optimum dietary proportions of lysine and tryptophan. The tryptophan "requirement" and the optimum lysine:tryptophan ratio were estimated for both adequate and subadequate lysine levels on the basis of weight gain, feed efficiency and changes in plasma levels of lysine, tryptophan and urea. The various criteria yielded similar estimates and indicated a tryptophan requirement of approximately 0.15% when lysine was adequate. The optimum lysine:tryptophan ratio was between 4 and 5 for the rapidly growing 3- to 6-week old rat.

Age Factors↗
PubMed1979

The effect of a low-protein ration on milk yield and plasma metabolites in Friesian heifers during early lactation.

1. Sixteen first-calf Friesian heifers were used in a continous treatment design experiment. For 2 weeks after calving they were given a 750 g concentrate, 250 g hay/kg ration with 169 g crude protein (nitrogen X 6.25; CP)/kg dry matter (DM). They were then divided into two groups of eight and given a high-protein (223 g CP/kg DM) or low-protein (107 g CP/kg DM) ration at the rate of 10.8 kg concentrate + 3.6 kg hay for 8 weeks. 2. Milk yield and composition, live weight and blood composition were monitored throughout. A digestibility trial was carried out with six animals on each treatment. 3. The low protein ration reduced DM, organic matter, energy and fibre digestibility significantly (P less than 0.001) so that intakes of digestible energy were not equal and the low-protein group lost more weight than the high-protein group. 4. Milk yield and the fat content of milk were lower in heifers given the low-protein ration (P less than 0.01). The lactose content of the milk was not affected and protein content only slightly reduced (P less than 0.01) by low-protein feeding. When the heifers were all changed onto an adequate protein (190 g CP/kg DM) ration in mid-lactation, those which had previously been under-fed protein appeared to recover in milk yield to the point they might have been expected to reach is given an adequate-protein ration throughout. 5. Concentrations of urea (P less than 0.001) and albumin (P less than 0.05) were reduced by underfeeding protein, but albumin concentration was affected less by diet than by stage of lactation. Blood concentrations of total protein, glucose, sodium, potassium, calcium, inorganic phosphate, iron, copper, haemoglobin and packed cell volume were unaffected by treatment. Blood magnesium concentration was slightly lower (P less than 0.01) with low-protein feeding.

Animals↗