• Journal of Veterinary Science
• /
• v.21 no.2
• /
• pp.23.1-23.10
• /
• 2020

The identification of biomarkers that distinguish diseased from healthy individuals is of great interest in human and veterinary fields. In this research area, a metabolomic approach and its related statistical analyses can be useful for biomarker determination and allow non-invasive discrimination of healthy volunteers from breast cancer patients. In this study, we focused on the most common canine neoplasm, mammary gland tumor, and herein, we describe a simple method using ultra-high-performance liquid chromatography to determine the levels of tyrosine and its metabolites (epinephrine, 3,4-dihydroxy-L-phenylalanine, 3,4-dihydroxyphenylacetic acid, and vanillylmandelic acid), tryptophan and its metabolites (5-hydroxyindolacetic acid, indoxyl sulfate, serotonin, and kynurenic acid) in canine mammary cancer urine samples. Our results indicated significantly increased concentrations of three tryptophan metabolites, 5-hydroxyindolacetic acid (p < 0.001), serotonin, indoxyl sulfate (p < 0.01), and kynurenic acid (p < 0.05), and 2 tyrosine metabolites, 3,4-dihydroxy-L-phenylalanine (p < 0.001), and epinephrine (p < 0.05) in urine samples from the mammary gland tumor group compared to concentrations in urine samples from the healthy group. The results indicate that select urinary tyrosine and tryptophan metabolites may be useful as non-invasive diagnostic markers as well as in developing a therapeutic strategy for canine mammary gland tumors.

• Journal of the Korean Magnetic Resonance Society
• /
• v.25 no.3
• /
• pp.33-38
• /
• 2021

Type 1 diabetes mellitus (T1DM) is caused by insufficient production of insulin, which is involved in carbohydrate metabolism. Type 2 diabetes mellitus (T2DM) has insulin resistance in which cells do not respond adequately to insulin. The purpose of this study was to estimate the characteristics of type 1 diabetes using streptozotocin-treated mice (STZ-mouse). The sera samples were collected from the models of hyperglycemic mouse and healthy mouse. Based on the pair-wise comparison, five metabolites were found to be noticeable: glucose, malonic acid, 3-hyroxybutyrate, methanol, and tryptophan. It was very natural glucose was upregulated in STZ-mouse. 3-hyroxybutyrate was also increased in the model. However, malonic acid, tryptophan, and methanol was downregulated in STZ-mouse. Several metabolites acetoacetate, acetone, alanine, arginine, asparagine, histidine, lysine, malate, methionine, ornithine, proline, propylene glycol, threonine, tyrosine, and urea tended to be varied in STZ-mouse while the statistical significance was not stratified for the variation. The multivariate model of PCA clearly showed the group separation between healthy control and STZ-mouse. The most significant metabolites that contributed the group separation included glucose, citrate, ascorbate, and lactate. Lactate did not show the statistical significance of change in t-test while it tends to down-regulated both in DNP and Diabetes.

• Asian-Australasian Journal of Animal Sciences
• /
• v.33 no.11
• /
• pp.1770-1778
• /
• 2020

Objective: This study was conducted to reveal potential metabolic differences of dairy cows fed corn stover (CS) and rice straw (RS) instead of alfalfa hay (AH) as main forage source. Methods: Thirty multiparous mid-late lactation Holstein dairy cows were selected and randomly assigned to three diets, AH, CS, or RS (n = 10). After 13 weeks of the feeding trial, coccygeal arterial and superficial epigastric venous plasma samples were collected before morning feeding for gas chromatography time-of-flight/mass spectrometry analyses. Results: In the artery, 8 and 13 metabolites were detected as differential metabolites between AH and CS, and between AH and RS, respectively. The relative abundance of phenylpropanoate (log₂fold change [FC]) = 1.30, 1.09), panthenol (log₂FC = 2.36, 2.20), threitol (log₂FC = 1.00, 1.07), and 3,7,12-trihydroxycoprostane (log₂FC = 0.79, 0.78) were greater in both CS and RS than in AH, and tyrosine (log₂FC = -0.32), phenylalanine (log₂FC = -0.30), and pyruvic acid (log₂FC = -0.30) were lower in RS than in AH. In the vein, 1 and 7 metabolites were detected as differential metabolites between AH and CS, and between AH and RS, respectively. By comparing AH and RS, we found that metabolic pathways of phenylalanine, tyrosine, and tryptophan biosynthesis and phenylalanine metabolism were enriched by integrative artery and vein analysis. Furthermore, AH and RS, arterial phenylpropanoate and 4-hydroxyproline were positively, and phenylalanine was negatively correlated with milk urea nitrogen. Finally, in AH and CS, arterial panthenol was negatively correlated with feed efficiency. Conclusion: Arterial metabolic profiles changed more than those in the veins from animals on three forage diets, differing in amino acids. We found that phenylalanine, tyrosine, and tryptophan biosynthesis and phenylalanine metabolism were restricted when cows were fed low-quality cereal straw diets.

• Journal of Microbiology and Biotechnology
• /
• v.19 no.10
• /
• pp.1142-1149
• /
• 2009

Several bioactive metabolites, including pyrrolnitrin, N-acylhomoserine lactones, and polyhydroxyalkanoates were isolated from Burkholderia sp. O33. Effects of various nutrients, including sugars, gluconolactone, glycerol, tryptophan, chloride, and zinc were investigated in relation to the production of these metabolites. Logarithmic increase of pyrrolnitrin was observed between 2-5 days and reached a maximum at 7-10 days. Tryptophan concentration reached the maximum at 3 days, whereas 7-chlorotryptophan was gradually increased throughout the studies. Among various carbon sources, gluconolactone, trehalose, and glycerol enhanced pyrrolnitrin production, whereas strong inhibitory effects were found with glucose. Relative concentrations of pyrrolnitrin and its precursors were in the order of pyrrolnitrin$\gg$dechloroaminopyrrolnitrin or aminopyrrolnitrin throughout the experiments. Among three N-acylhomoserine lactones, the N-octanoyl analog was the most abundant quorum sensing signal, of which the concentrations reached the maximum in 2-3 days, followed by a rapid dissipation to trace level. No significant changes in pyrrolnitrin biosynthesis were observed by external addition of N-acylhomoserine lactones. Polyhydroxyalkanoates accumulated up to 3-4 days and decreased slowly thereafter. According to the kinetic analyses, no strong correlations were found between the levels of pyrrolnitrin, N-acylhomoserine lactones, and polyhydroxyalkanoates.

• The Korean Journal of Zoology
• /
• v.34 no.2
• /
• pp.203-208
• /
• 1991

Body weight gain in the niadn deficient group of quail was markedly lowered as compared to that of the control group, but heart, kidney and liver weight were slighdy reduced reladve to the body weight. Nicotinic acid deficiency resulted in the significant increase of serum glucose level but the serum cholesterol, albumin and total protein levels were not affected to any extent. Glutamic oxaloacetate iransaminase and glutamic pyruvate transaminase activities were significandy enhanced but alkaline phosphatase and lactic dehydrogenase activities were not influenced. Tryptophan and tyrosine levels were remarkably reduced and a similar observation was also made with aspartic acid, glutamic acid and alanine plus serine. However, the levels of basic amino acids such as arginine, histidine and lysine plus branched chain amino acids such as isoleucine, leucine and valine were not affected.

• Journal of Microbiology and Biotechnology
• /
• v.33 no.12
• /
• pp.1657-1670
• /
• 2023

This study aimed to evaluate the effects of Limosilactobacillus fermentum and Lactiplantibacillus plantarum isolated from human feces coordinating with inulin on the composition of gut microbiota and metabolic profiles in db/db mice. These supplements were administered to db/db mice for 12 weeks. The results showed that the Lactobacillaceae coordinating with inulin group (LI) exhibited lower fasting blood glucose levels than the model control group (MC). Additionally, LI was found to enhance colon tissue and increase the levels of short-chain fatty acids. 16S rRNA sequencing revealed that the abundance of Corynebacterium and Proteus, which were significantly increased in the MC group compared with NC group, were significantly decreased by the treatment of LI that also restored the key genera of the Lachnospiraceae_NK4A136_group, Lachnoclostridium, Ruminococcus_gnavus_group, Desulfovibrio, and Lachnospiraceae_UCG-006. Untargeted metabolomics analysis showed that lotaustralin, 5-hydroxyindoleacetic acid, and 13(S)-HpODE were increased while L-phenylalanine and L-tryptophan were decreased in the MC group compared with the NC group. However, the intervention of LI reversed the levels of these metabolites in the intestine. Correlation analysis revealed that Lachnoclostridium and Ruminococcus_gnavus_group were negatively correlated with 5-hydroxyindoleacetic acid and 13(S)-HpODE, but positively correlated with L-tryptophan. 13(S)-HpODE was involved in the "linoleic acid metabolism". L-tryptophan and 5-hydroxyindoleacetic acid were involved in "tryptophan metabolism" and "serotonergic synapse". These findings suggest that LI may alleviate type 2 diabetes symptoms by modulating the abundance of Ruminococcus_gnavus_group and Lachnoclostridium to regulate the pathways of "linoleic acid metabolism", "serotonergic synapse", and" tryptophan metabolism". Our results provide new insights into prevention and treatment of type 2 diabetes.

• Biomolecules & Therapeutics
• /
• v.32 no.4
• /
• pp.403-423
• /
• 2024

The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut microbiome plays a crucial role in maintaining the body's equilibrium and has recently been discovered to influence the functioning of the central nervous system (CNS). The communication between the nervous system and the GI tract occurs through a two-way network called the gut-brain axis. The nervous system and the GI tract can modulate each other through activated neuronal cells, the immune system, and metabolites produced by the gut microbiome. Extensive research both in preclinical and clinical realms, has highlighted the complex relationship between the gut and diseases associated with the CNS, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review aims to delineate receptor and target enzymes linked with gut microbiota metabolites and explore their specific roles within the brain, particularly their impact on CNS-related diseases.

• Journal of Plant Biotechnology
• /
• v.42 no.3
• /
• pp.186-195
• /
• 2015

Anthranilate synthase (AS) is a key enzyme in the biosynthesis of tryptophan (Trp), which is the precursor of bioactive metabolites like indole-3-acetic acid and other indole alkaloids. Alpha anthranilate synthase 2 (OsASA2) plays a critical role in the feedback inhibition of tryptophan biosynthesis. In this study, two vectors with single (F124V) and double (S126F/L530D) point mutations of the OsASA2 gene for feedback-insensitive ${\alpha}$ subunit of rice anthranilate synthase were constructed and transformed into wildtype Dongjinbyeo by Agrobacterium-mediated transformation. Transgenic single and double mutant lines were selected as a single copy using TaqMan PCR utilized nos gene probe. To select intergenic lines, the flanking sequence of RB or LB was digested with a BfaI enzyme. Four intergenic lines were selected using a flanking sequence tagged (FST) analysis. Expression in rice (Oryza sativa L.) of the transgenes resulted in the accumulation of tryptophan (Trp), indole-3-acetonitrile (IAN), and indole-3-acetic acid (IAA) in leaves and tryptophan content as a free amino acid in seeds also increased up to 30 times relative to the wildtype. Two homozygous event lines, S-TG1 and D-TG1, were selected for characterization of agronomic traits and metabolite profiling of seeds. Differentially expressed genes (DEGs), related to ion transfer and nutrient supply, were upregulated and DEGs related to co-enzymes that work as functional genes were down regulated. These results suggest that two homozygous event lines may prove effective for the breeding of crops with an increased level of free tryptophan content.

• The Korean Journal of Physiology and Pharmacology
• /
• v.28 no.2
• /
• pp.153-164
• /
• 2024

This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control. Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 10¹¹ colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5-6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.

• Journal of Ginseng Research
• /
• v.47 no.1
• /
• pp.54-64
• /
• 2023

Background: Panax ginseng Meyer (P. ginseng) is a traditional natural/herbal medicine. The amelioration on inflammatory bowel disease (IBD) activity rely mainly on its main active ingredients that are referred to as ginsenosides. However, the current literature on gut microbiota, gut microbiota-host co-metabolites, and systems pharmacology has no studies investigating the effects of ginsenoside on IBD. Methods: The present study was aimed to investigate the role of ginsenosides and the possible underlying mechanisms in the treatment of IBD in an acetic acid-induced rat model by integrating metagenomics, metabolomics, and complex biological networks analysis. In the study ten ginsenosides in the ginsenoside fraction (GS) were identified using Q-Orbitrap LC-MS. Results: The results demonstrated the improvement effect of GS on IBD and the regulation effect of ginsenosides on gut microbiota and its co-metabolites. It was revealed that 7 endogenous metabolites, including acetic acid, butyric acid, citric acid, tryptophan, histidine, alanine, and glutathione, could be utilized as significant biomarkers of GS in the treatment of IBD. Furthermore, the biological network studies revealed EGFR, STAT3, and AKT1, which belong mainly to the glycolysis and pentose phosphate pathways, as the potential targets for GS for intervening in IBD. Conclusion: These findings indicated that the combination of genomics, metabolomics, and biological network analysis could assist in elucidating the possible mechanism underlying the role of ginsenosides in alleviating inflammatory bowel disease and thereby reveal the pathological process of ginsenosides in IBD treatment through the regulation of the disordered host-flora co-metabolism pathway.