Serum Amino Acid Research Articles

Dietary sodium sulphate supplementation during mid-to-late gestation improves placental angiogenesis, bile acid metabolism, and serum amino acid concentrations of sows

Sulphate plays a vital role in the growth and development of the foetus. Sodium sulphate (Na2SO4) is utilised as a dietary protein nutrient factor and helps replenish sulphur elements in livestock and poultry. Therefore, this study aimed to investigate the effects of Na2SO4 supplementation in mid to late pregnancy on bile acid metabolism, amino acid metabolism, placental vascular development and antioxidant capacity of sows. At day 1 of gestation (G1), a total of twenty-six primiparous sows were carefully chosen and randomised into two groups: (1) control group, (2) Na2SO4 group (1.40 g/kg). Blood samples and placentas from sows were collected to measure biochemistry parameters, antioxidant indexes, placental vascular density, and indicators related to bile acid metabolism and amino acid concentrations, respectively. We found that dietary supplementation with Na2SO4 had a tendency for a reduction of incidence of stillborn at farrowing. Further observation showed that sows supplemented with Na2SO4 had decreased total bile acid level in cord blood, and increased placental gene expression of sulphotransferase and organic anion transport peptide. Na2SO4 supplementation increased catalase and total superoxide dismutase activity in cord blood, decreased placental malondialdehyde content, and enhanced placental protein expression of Sirtuin 1. Moreover, Na2SO4 consumption resulted in increased vascular density of placental stroma and elevated amino acid levels in sows and cord blood. Furthermore, maternal Na2SO4 consumption reduced serum urea concentrations of sows and umbilical cord blood at G114. In addition, dietary supplementation with Na2SO4 activated the protein expression of the placental mechanistic target of rapamycin complex 1. Collectively, these findings indicated that maternal supplementation with Na2SO4 during mid-to-late gestation elevated foetal survival via improving placental angiogenesis, bile acid metabolism and amino acid utilisation.

Automated Liquid Handling Extraction and Rapid Quantification of Underivatized Amino Acids and Tryptophan Metabolites from Human Serum and Plasma Using Dual-Column U(H)PLC-MRM-MS and Its Application to Prostate Cancer Study.

Amino acids (AAs) and their metabolites are important building blocks, energy sources, and signaling molecules associated with various pathological phenotypes. The quantification of AA and tryptophan (TRP) metabolites in human serum and plasma is therefore of great diagnostic interest. Therefore, robust, reproducible sample extraction and processing workflows as well as rapid, sensitive absolute quantification are required to identify candidate biomarkers and to improve screening methods. We developed a validated semi-automated robotic liquid extraction and processing workflow and a rapid method for absolute quantification of 20 free, underivatized AAs and six TRP metabolites using dual-column U(H)PLC-MRM-MS. The extraction and sample preparation workflow in a 96-well plate was optimized for robust, reproducible high sample throughput allowing for transfer of samples to the U(H)PLC autosampler directly without additional cleanup steps. The U(H)PLC-MRM-MS method, using a mixed-mode reversed-phase anion exchange column with formic acid and a high-strength silica reversed-phase column with difluoro-acetic acid as mobile phase additive, provided absolute quantification with nanomolar lower limits of quantification within 7.9 min. The semi-automated extraction workflow and dual-column U(H)PLC-MRM-MS method was applied to a human prostate cancer study and was shown to discriminate between treatment regimens and to identify metabolites responsible for discriminating between healthy controls and patients on active surveillance.

Taurine improves juvenile Seriola rivoliana growth performance and biochemical profiles in blood serum and skeletal muscle

Taurine supplementation has shown survival and feeding efficiency in larval fish development. Thus, the present study aims to evaluate the effects of adding taurine to the longfin yellowtail (Seriola rivoliana) diet for 60 days. Fish (n = 270) were distributed in three treatments: T0 without taurine, T1, and T2, supplemented with taurine at 1 and 2%, respectively. Growth performance, blood serum biochemistry, fatty acid, and amino acid profiles in skeletal muscle were evaluated. Notable improvements (P < 0.05) were observed in T1 and T2 in terms of specific growth rate (SGR) and weight gain (WG). Survival rates (SR) did not show significant differences (P > 0.05). In addition, a decrease was observed in intraperitoneal fat (IPF). Still, an increase was observed in blood parameters, including higher total protein (TP) and globulin (GLO) concentration, as well as a reduction in cholesterol (CHO) levels. Changes in fatty acid profiles were also detected in skeletal muscle with an increase in omega-3 fatty acids (EPA and DHA) and elevation in taurine concentration in T2. The results showed that adding 20 g kg-1 of taurine to the diet improved growth, skeletal muscle, and blood serum biochemistry. Therefore, the use of higher taurine concentrations is recommended in future studies to understand fully the extent of the benefits to longfin yellowtail juveniles.

Association between Childhood Overweight and Altered Concentrations of Circulating Amino Acids.

(1) Background: Dysregulated serum amino acids (AA) are known to be associated with obesity and risk of Type 2 Diabetes (T2D) in adults, and recent studies support the same notion in the pubertal age. It is, however, unknown whether childhood overweight may already display alterations of circulating AA. (2) Methods: We used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS)-targeted metabolomics to determine plasma concentrations of AA and AA-related molecules in 36 children aged 7-12 years with normal weight or overweight. Clinical and anthropometric parameters were measured. (3) Results: Overweight in children is associated with an altered AA profile, with increased branched-chain amino acids (BCAA) and decreased glycine levels, with no clinically manifested metabolic conditions. Moreover, z-BMI was positively and negatively correlated with BCAA and glycine levels, respectively, even after adjustment for age and gender. We also found a correlation between the AA profile and clinical parameters such as lipids profile and glycemia. (4) Conclusions: A pattern of low glycine, and increased BCAA is correlated to z-BMI, total cholesterol, and triglycerides in overweight but otherwise healthy children. Our data suggest that, in childhood overweight, AA disturbances may precede other clinical parameters, thus providing an early indicator for the later development of metabolic disease.

Cellular metabolism and hypoxia interfacing with allergic diseases.

Allergic diseases display significant heterogeneity in their pathogenesis. Understanding the influencing factors, pathogenesis, and advancing new treatments for allergic diseases is becoming more and more vital as currently, prevalence continues to rise, and mechanisms of allergic diseases are not fully understood. The upregulation of the hypoxia response is linked to an elevated infiltration of activated inflammatory cells, accompanied by elevated metabolic requirements. An enhanced hypoxia response may potentially contribute to inflammation, remodeling, and the onset of allergic diseases. It has become increasingly clear that the process underlying immune and stromal cell activation during allergic sensitization requires well-tuned and dynamic changes in cellular metabolism. The purpose of this review is to examine current perspectives regarding metabolic dysfunction in allergic diseases. In the past decade, new technological platforms such as "omic" techniques have been applied, allowing for the identification of different biomarkers in multiple models ranging from altered lipid species content, increased nutrient transporters, and altered serum amino acids in various allergic diseases. Better understanding, recognition, and integration of these alterations would increase our knowledge of pathogenesis and potentially actuate a novel repertoire of targeted treatment approaches that regulate immune metabolic pathways.

Exploring altered free amino acids and metabolites: Insights into the metabolic landscape of preeclampsia

IntroductionPreeclampsia (PE) is a complex disease that poses a risk for maternal and perinatal morbidity and mortality. This study aimed to investigate the role of maternal serum amino acids (AAs) levels in PE. Materials and methodsA total of 56 pregnant women (26 with PE and 30 controls) were included in the study. The participants had a confirmed gestational age between 24 and 37 weeks. The mean body mass index (BMI) for the PE group was 33.1 kg/m2, while the control group had a mean BMI of 29.6 kg/m2. AAs levels were quantified, and statistical analyses were performed to identify significant differences between the two groups. Receiver Operating Characteristic (ROC) curve analysis was employed the diagnostic potential of specific AAs. ResultsWe observed significantly elevated levels of multiple AAs in the PE group, including citrulline, lysine, ethanolamine, ornithine and histidine. Citrulline exhibited exceptional predictive power for PE with 100.0% sensitivity and specificity at a cutoff of 7.79 µmol/L, reflected in an area under the curve (AUC) of 1.000. DiscussionOur study highlights the crucial involvement of altered amino acid levels, specifically in the urea cycle, disruptions in lysine and ethanolamine metabolism in PE development. Exploring these changes may reveal new therapeutic targets, providing insights into the disease's molecular mechanisms. Understanding amino acid metabolism in PE not only informs therapeutic strategies but also holds the potential to revolutionize early diagnosis and intervention.

A Case Report of a Patient with Pyruvate Carboxylase Deficiency

Background: Pyruvate carboxylase catalyzes the carboxylation of pyruvate to oxaloacetate, a crucial intermediate of the tricarboxylic acid (TCA) cycle and the initial step in converting pyruvate to glucose (gluconeogenesis). Pyruvate carboxylase deficiency is a rare metabolic disorder characterized by lactic acidosis, failure to thrive, development delay, and recurrent seizures at an early age in severely affected patients. The onset and severity of pyruvate carboxylase deficiency have been classified as severe neonatal (type B), usually fatal, less severe infantile (type A), compatible with survival but with impaired neurologic development, and milder, later onset (type C) with some residual impairment. Clinical manifestations include hypotonia, mixed hypertonia, ataxia, choreoathetosis, microcephaly, and other signs of impaired white matter development. Case Report: A 7-day-old baby with a birth weight of 3kg, born to related parents, presented with clinical symptoms such as lethargy, poor feeding, and grunting since birth. Additionally, he experienced a drop in O2 saturation and cyanosis during his hospitalization. Test results revealed lactic acidosis and hyperammonemia. Furthermore, serum amino acids chromatography- HPLC indicated an increase in lysine and citrulline. The patient succumbed after 16 days due to multi-organ damage. Genetic analysis identified pyruvate carboxylase enzyme deficiency. Conclusion: Pyruvate carboxylase deficiency is a rare inborn error of metabolism that can lead to developmental delay and failure to thrive, typically beginning in the neonatal or early infantile period. The possibility of pyruvate carboxylase deficiency should be considered in any child presenting with lactic acidosis and neurological abnormalities, particularly if associated with hypoglycemia, hyperammonemia, or ketosis.

Targeted metabolomic profiles of serum amino acids are independently correlated with malnutrition in older adults.

Malnutrition is a common geriatric syndrome that is closely associated with adverse clinical outcomes and poses significant harm to older adults. Early assessment of nutritional status plays a crucial role in preventing and intervening in cases of malnutrition. However, there is currently a lack of measurable methods and biomarkers to evaluate malnutrition in older adults accurately. The aim of this study is to investigate the independent correlation between serum levels of amino acids and malnutrition in older adults, and to identify effective metabolomics biomarkers that can aid in the early detection of geriatric malnutrition. A total of 254 geriatric medical examination participants from Beijing Hospital were included in the study, consisting of 182 individuals with normal nutritional status (Normal group) and 72 patients at risk of malnutrition or already malnourished (MN group). Malnutrition was assessed using the Mini-Nutritional Assessment Short-Form (MNA-SF). Demographic data were collected, and muscle-related and lipid indexes were determined. Serum amino acid concentrations were measured using isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS). The correlation between serum amino acid levels and malnutrition was analyzed using non-parametric tests, partial correlation analysis, linear regression, and logistic regression. The geriatric MN group exhibited significantly lower serum aromatic amino acid levels (P < 0.05) compared to the normal group. A positive correlation was observed between serum aromatic amino acid levels and the MNA-SF score (P = 0.002), as well as with known biomarkers of malnutrition such as body mass index (BMI) (P < 0.001) and hemoglobin (HGB) (P = 0.005). Multivariable logistic or linear regression analyses showed that aromatic amino acid levels were negatively correlated with MN and positively correlated with the MNA-SF score, after adjusting for some confounding factors, such as age, gender, BMI, smoking status, history of dyslipidemia, diabetes mellitus and frailty. Stratified analyses revealed that these trends were more pronounced in individuals without a history of frailty compared to those with a history of frailty, and there was an interaction between aromatic amino acid levels and frailty history (P = 0.004). Our study suggests that serum aromatic amino acids are independently associated with malnutrition in older adults. These results have important implications for identifying potential biomarkers to predict geriatric malnutrition or monitor its progression and severity, as malnutrition can result in poor clinical outcomes.

Blood Serum Amino Acid Pool of European Migratory Chiroptera Vespertilio murinus Linnaeus, 1758 and Pipistrellus nathusii Keyserling et Blasius, 1839 of the Ural Fauna.

The pool of free amino acids (AAs) in the blood serum was studied in two European migratory bat species, Vespertilio murinus and Pipistrellus nathusii, of the Urals. Bats from this year's bloods were examined, and significant differences were observed in main metabolic groups of free AAs, including glycogenic (GGAAs), nonessential (NEAAs), essential (EAAs), and sulfur-containing (SCAAs) AAs (p < 0.05). Based on the percent content of the metabolic groups in the total AA pool, GGAAs (79.7%) and EAAs (49.4%) were found to predominate in P. nathusii, and GGAAs (74.9%) and NEAAs (58.4%), in V. murinus. No difference in AAA and BCAA contents was observed between V. murinus and P. nathusii (p > 0.05). The migratory species were shown to significantly differ in the metabolic groups of serum AAs from the resident species Myotis dasycneme (p < 0.05).

Pharmacokinetics of L-theanine and the effect on amino acid composition in mice administered with L-theanine

L-theanine, an amino acid component of the tea leaves of Camellia sinensis, is sold in Japan as a supplement for good sleep. Although several studies in humans and mice have reported the effects of L-theanine on brain function, only a few reports have comprehensively clarified the disposition of theanine administered to mice and its effects on concentrations of other blood amino acids. In this study, we aimed to determine the changes in the blood levels of L-theanine administered to mice and amino acid composition of the serum. L-theanine were administered to four-week-old Std-ddY male mice orally or via tail vein injection. L-theanine and other amino acids in serum prepared from blood collected at different time points post-dose were labeled with phenylisothiocyanate and quantified. The serum concentration of orally administered L-theanine peaked 15 min after administration. The area under the curve for tail vein injection revealed the bioavailability of L- theanine to be approximately 70%. L-theanine administration did not affect any amino acid levels in the serum, but a significant increase in the peak area overlapping the Glycine (Gly) peak was observed 30 min after administration. L-theanine administered to mice was rapidly absorbed and eliminated, suggesting that taking L-theanine as a supplement is safe without affecting its own levels or serum levels of other amino acids. However, considering that Gly, similar to L-theanine, is used as a dietary supplement for its anxiolytic effects and to improve sleep, determining the effects of L-theanine administration on Gly is important and needs further research.

Unravelling genetic architecture of circulatory amino acid levels, and their effect on risk of complex disorders.

Variations in serum amino acid levels are linked to a multitude of complex disorders. We report the largest genome-wide association study (GWAS) on nine serum amino acids in theUK Biobank participants (117944, European descent). We identified 34 genomic loci for circulatory levels of alanine, 48 loci for glutamine, 44 loci for glycine, 16 loci for histidine, 11 loci for isoleucine, 19 loci for leucine, 9 loci for phenylalanine, 32 loci for tyrosine and 20 loci for valine. Our gene-based analysis mapped 46-293 genes associated with serum amino acids, including MIP,GLS2, SLCgene family, GCKR, LMO1, CPS1and COBLL1.The gene-property analysis across 30 tissues highlighted enriched expression of the identified genes in liver tissues for all studied amino acids, except for isoleucine and valine, in muscle tissues for serum alanine and glycine, in adrenal gland tissues for serum isoleucine and leucine, and in pancreatic tissues for serum phenylalanine. Mendelian randomization (MR) phenome-wide association studyanalysis and subsequent two-sample MR analysis provided evidence that every standard deviation increase in valine is associated with 35% higher risk of type 2 diabetes and elevated levels of serum alanine and branched-chain amino acidswith higher levels of total cholesterol, triglyceride andlow-density lipoprotein, and lower levels ofhigh-density lipoprotein. In contrast to reports by observational studies, MR analysis did not support a causal association between studied amino acids and coronary artery disease, Alzheimer's disease, breast canceror prostate cancer. In conclusion, we explored the genetic architecture of serum amino acids and provided evidence supporting a causal role of amino acids in cardiometabolic health.

Mulberry leaf and konjac flour compound dietary fiber improves digestion and metabolism in elderly mice with high-fish-protein diet by regulating gut microbiota structure and intestinal tissue repair

Ensuring sufficient protein intake, efficient digestion, and optimal absorption are crucial for the elderly. This study aims to investigate the potential of a compound dietary fiber, consisting of mulberry leaf and konjac flour (CMK), to enhance the digestion and absorption of a high-fish-protein diet in elderly mice. Results showed that CMK effectively reduced the number of unique peptide segments, generated short-chain fatty acids (SCFA) in feces, improved the content of glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), amino acid, and urea nitrogen in serum, activated the contents of pepsin, trypsin, and erepsin, and enhanced the expression of glutamate dehydrogenase (GDH), peptide transporter 1 (PepT1), and aminopeptidase N (APN). Furthermore, CMK demonstrated its ability to decrease the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-10 (IL-10), lipopolysaccharide (LPS), and lipopolysaccharide binding protein (LBP), while increase the abundance of beneficial bacteria, such as Lactobacillus and Blautia. In conclusion, CMK proved effective in enhancing the digestion and metabolism of protein in elderly mice through the regulation of gut microbiota structure and intestinal tissue repair.

Description of the fasted serum metabolomic signature of lean and obese cats at maintenance and of obese cats under energy restriction.

This study aimed to investigate the serum metabolomic profile of obese and lean cats as well as obese cats before and after energy restriction for weight loss. Thirty cats, 16 obese (body condition score 8 to 9/9) and 14 lean (body condition score 4 to 5/9), were fed a veterinary weight loss food during a 4-week period of weight maintenance (L-MAINT and O-MAINT). The 16 obese cats were then energy restricted by a 60% energy intake reduction with the same food for a 10-week period (O-RESTRICT). Fasted serum metabolites were measured using nuclear magnetic resonance and direct infusion mass spectrometry after the maintenance period for L-MAINT and O-MAINT cats and after the energy restriction period for O-RESTRICT and compared between groups using a two-sided t-test. Obese cats lost 672 g ± 303 g over the 10-week restriction period, representing a weight loss rate of 0.94 ± 0.28% per week. Glycine, l-alanine, l-histidine, l-glutamine, 2-hydroxybutyrate, isobutryric acid, citric acid, creatine, and methanol were greater in O-RESTRICT compared to O-MAINT. There was a greater concentration of long-chain acylcarnitines in O-RESTRICT compared to both O-MAINT and L-MAINT, and greater total amino acids compared to O-MAINT. Glycerol and 3-hydroxybutyric acid were greater in O-MAINT compared to L-MAINT, as were several lysophosphatidylcholines. Thus, energy restriction resulted in increased dispensable amino acids in feline serum which could indicate alterations in amino acid partitioning. An increase in lipolysis was not evident, though greater circulating acylcarnitines were observed, suggesting that fatty acid oxidation rates may have been greater under calorie restriction. More research is needed to elucidate energy metabolism and substrate utilization, specifically fatty acid oxidation and methyl status, during energy restriction in strict carnivorous cats to optimize weight loss.

Targeted metabolomic analysis of serum amino acids in heart failure patients

Heart failure (HF) has been recognized as a global epidemic with high rates of morbidity, hospitalization, and mortality. The role of amino acids, which provide the body with energy, in the development of HF is still unclear. The aim of this study was to explore changes in serum amino acids in patients with HF and identify potential biomarkers. First, the serum amino acid metabolism profiles of 44 patients with HF and 30 healthy controls (Con) were quantitatively measured. Then, candidate markers were identified through the utilization of T test, multivariate statistical analysis, and receiver operating characteristic (ROC) curve analysis. The results found that there were 11 amino acid levels that were significantly different between patients with HF and Con. Based on ROC curve analysis, the biomarkers of eight amino acids (Glutamic acid, Taurine, l-aspartic acid, l-ornithine, Ethanolamine, l-Serine, l-Sarcosine, and Cysteine) showed high sensitivity and specificity (AUC > 0.90), and binary logistic regression analysis was used in MetaboAnalyst 5.0. Among the amino acids examined, six exhibited notable alterations in accordance with the severity of HF. In conclusion, this study cannot only provide clinicians with an objective diagnostic approach for the early identification of HF, but also enhances comprehension of the underlying mechanisms involved in the pathogenesis of HF.

Changes in FeNO, d-ROMs, and BH4 by Intravenous L-Arginine in Children and Its Putative Role in Asthma Treatment.

Pteridines are metabolites of tetrahydrobiopterin (BH4), being coenzymes for nitric oxide synthase (NOS). No study has clarified the relationship among pteridines and NOS, fractional exhaled nitric oxide (FeNO) generated by pteridines, and reactive oxygen species. In this study, we administered arginine, a precursor of NO, and confirmed changes in the levels of pteridines, FeNO, and reactive oxygen species and their relationship to clarify the pathogenesis of airway inflammation in which oxidative stress is involved, such as bronchial asthma. This is a prospective, randomized open-label study. Children, aged 2 to 15 years, who were scheduled for growth hormone stimulation tests and were able to undergo a respiratory function test were recruited. They were randomly divided into two groups: arginine-administered and control groups. In the former, L-arginine hydrochloride was intravenously administered. After administration, the levels of diacron-reactive oxygen metabolites (d-ROMs), serum pteridines, serum amino acids, and fractional exhaled NO (FeNO) were measured. We analyzed 15 children aged 4 to 14 years. In the arginine-administered group, there was an increase in the FeNO level and a decrease in the d-ROMs level, reaching a peak 30 min after administration, compared with the control group. In addition, there was a decrease in the serum biopterin level and an increase in the d-ROMs level, reaching peak 60 min after administration. The administration of L-arginine increased the NO level and decreased the d-ROMs level. Due to this, biopterin may be consumed and decreased, leading to an increase in the d-ROMs level. As a reduction in reactive oxygen species leads to the relief of inflammation, arginine and biopterin may be useful for inhibiting inflammation.

Genetic risk score for insulin resistance based on gene variants associated to amino acid metabolism in young adults.

Circulating concentration of arginine, alanine, aspartate, isoleucine, leucine, phenylalanine, proline, tyrosine, taurine and valine are increased in subjects with insulin resistance, which could in part be attributed to the presence of single nucleotide polymorphisms (SNPs) within genes associated with amino acid metabolism. Thus, the aim of this work was to develop a Genetic Risk Score (GRS) for insulin resistance in young adults based on SNPs present in genes related to amino acid metabolism. We performed a cross-sectional study that included 452 subjects over 18 years of age. Anthropometric, clinical, and biochemical parameters were assessed including measurement of serum amino acids by high performance liquid chromatography. Eighteen SNPs were genotyped by allelic discrimination. Of these, ten were found to be in Hardy-Weinberg equilibrium, and only four were used to construct the GRS through multiple linear regression modeling. The GRS was calculated using the number of risk alleles of the SNPs in HGD, PRODH, DLD and SLC7A9 genes. Subjects with high GRS (≥ 0.836) had higher levels of glucose, insulin, homeostatic model assessment- insulin resistance (HOMA-IR), total cholesterol and triglycerides, and lower levels of arginine than subjects with low GRS (p < 0.05). The application of a GRS based on variants within genes associated to amino acid metabolism may be useful for the early identification of subjects at increased risk of insulin resistance.

Dietary fat and high energy density diet: Influence on intestinal health, oxidative stressand performance of weaned piglets.

The utilization of dietary components to support gut function and the health of young animals is an important factor for improved performance. The influence of high dietary fat levels in a lowor high energy density diet on the performance of weaned piglets in relation to intestinal absorptive function, amino acid utilization, oxidative stress, and microbial metabolites was assessed in this study. The study examined the effect of two different diets containing either a low energy density/high-fat level or a high energy density/high-fat level. A total of 16 healthy weaners (9.60 ± 0.13 kg) were allocated to one of the two dietary treatments. There were eight weaners per treatment. Results showed that feed intake and body weight gain of weaners were increased by the diet of high energy density/high-fat level (p < 0.05), but the feed efficiency showed an increased tendency of significance (p = 0.05). In the duodenum, the villus height(VH) and VH/crypt depth (CD) ratio (VH:CD) were increased by dietary high energy density/high fat. In the jejunum and ileum, the CD was increased by low energy density/high-fat diet, while the goblet cell count and VH:CD were increased by dietary high energy density/high-fat level. Methionine, lysineand phenylalanine concentrations were increased by high energy density/high-fat diet while low energy density/high-fat diet showed an increased tendency to increase citrulline and ornithine concentrations in the piglet. Oxidative stress marker, lactase enzyme activity and serum calcium concentration were increased by a high energy density/high-fat diet. Increased dietary fat in all diets induced diarrhoea in the weaners (p < 0.01). It was concluded that a dietary high energy density/high-fat diet seems to positively modulate gut absorptive function, serum amino acid (methionine and lysine), calcium levels and increased oxidative stress markers in the weaned piglets.

Using an Interpretable Amino Acid-Based Machine Learning Method to Enhance the Diagnosis of Major Depressive Disorder.

Background: Major depressive disorder (MDD) is a leading cause of disability worldwide. At present, however, there are no established biomarkers that have been validated for diagnosing and treating MDD. This study sought to assess the diagnostic and predictive potential of the differences in serum amino acid concentration levels between MDD patients and healthy controls (HCs), integrating them into interpretable machine learning models. Methods: In total, 70 MDD patients and 70 HCs matched in age, gender, and ethnicity were recruited for the study. Serum amino acid profiling was conducted by means of chromatography-mass spectrometry. A total of 21 metabolites were analysed, with 17 from a preset amino acid panel and the remaining 4 from a preset kynurenine panel. Logistic regression was applied to differentiate MDD patients from HCs. Results: The best-performing model utilised both feature selection and hyperparameter optimisation and yielded a moderate area under the receiver operating curve (AUC) classification value of 0.76 on the testing data. The top five metabolites identified as potential biomarkers for MDD were 3-hydroxy-kynurenine, valine, kynurenine, glutamic acid, and xanthurenic acid. Conclusions: Our study highlights the potential of using an interpretable machine learning analysis model based on amino acids to aid and increase the diagnostic accuracy of MDD in clinical practice.

Gut microbiome and serum amino acid metabolome alterations in autism spectrum disorder

Gut microbiota and their metabolic products might play important roles in regulating the pathogenesis of autism spectrum disorder (ASD). The purpose of this study was to characterize gut microbiota and serum amino acid metabolome profiles in children with ASD. A non-randomized controlled study was carried out to analyze the alterations in the intestinal microbiota and their metabolites in patients with ASD (n = 30) compared with neurotypical controls (NC) (n = 30) by metagenomic sequencing to define the gut microbiota community and liquid chromatography/mass spectrometry (LC/MS) analysis to characterize the metabolite profiles. Compared with children in the NC group, those in the ASD group showed lower richness, higher evenness, and an altered microbial community structure. At the class level, Deinococci and Holophagae were significantly lower in children with ASD compared with TD. At the phylum level, Deinococcus-Thermus was significantly lower in children with ASD compared with TD. In addition, the functional properties (such as galactose metabolism) displayed significant differences between the ASD and NC groups. Five dominant altered species were identified and analyzed (LDA score > 2.0, P < 0.05), including Subdoligranulum, Faecalibacterium_praushitzii, Faecalibacterium, Veillonellaceae, and Rumminococcaceae. The peptides/nickel transport system was the main metabolic pathway involved in the differential species in the ASD group. Decreased ornithine levels and elevated valine levels may increase the risk of ASD through a metabolic pathway known as the nickel transport system. The microbial metabolism in diverse environments was negatively correlated with phascolarctobacterium succinatutens. Our study provides novel insights into compositional and functional alterations in the gut microbiome and metabolite profiles in ASD and the underlying mechanisms between metabolite and ASD.

Maternal serum amino acids and hydroxylated sphingomyelins at pregnancy are associated with anxiety symptoms during pregnancy and throughout the first year after delivery

BackgroundStudies suggest an interplay between maternal metabolome and mental health. ObjectiveWe investigated the association of maternal serum metabolome at pregnancy with anxiety scores during pregnancy and throughout the first year postpartum. MethodsA prospective cohort of Brazilian women collected 119 serum metabolome at pregnancy (28–38 weeks) and anxiety scores measured by the State-Trait Anxiety Inventory (STAI) at pregnancy (n = 118), 1 (n = 83), 6 (n = 68), and 12 (n = 57) months postpartum. Targeted metabolomics quantified metabolites belonging to amino acids (AA), biogenic amines/amino acid-related compounds, acylcarnitines, lysophosphatidylcholines, diacyl phosphatidylcholines, alkyl:acyl phosphatidylcholines, non-hydroxylated and hydroxylated sphingomyelins [SM(OH)], and hexoses classes. Linear mixed-effect models were used to evaluate the association of metabolites and STAI scores. Hierarchical clustering and principal component analyses were employed to identify clusters and metabolites, which drove their main differences. Multiple comparison-adjusted p-values (q-value) ≤ 0.05 were considered significant. ResultsAA (β = −1.44) and SM(OH) (β = −1.49) classes showed an association with STAI scores trajectory (q-value = 0.047). Two clusters were identified based on these classes. Women in cluster 2 had decreased AA and SM(OH) concentrations and higher STAI scores (worse symptoms) trajectory (β = 2.28; p-value = 0.041). Isoleucine, leucine, valine, SM(OH) 22:1, 22:2, and 24:1 drove the main differences between the clusters. LimitationsThe target semiquantitative metabolome analysis and small sample size limited our conclusions. ConclusionsOur results suggest that AA and SM(OH) during pregnancy play a role in anxiety symptoms throughout the first year postpartum.