Studies on Tryptophan Metabolites in Patients of Major Monopolar Depression

Immunomodulatory Roles of Tryptophan Metabolites in Inflammation and Cancer

10.3389/978-2-88963-984-7 ◽

2020 ◽

Keyword(s):

Tryptophan Metabolites

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High-Resolution Metabolomics of 50 Neurotransmitters and Tryptophan Metabolites in Feces, Serum, and Brain Tissues Using UHPLC-ESI-Q Exactive Mass Spectrometry

ACS Omega ◽

10.1021/acsomega.0c05789 ◽

2021 ◽

Author(s):

Yunjia Lai ◽

Chih-Wei Liu ◽

Liang Chi ◽

Hongyu Ru ◽

Kun Lu

Keyword(s):

Mass Spectrometry ◽

High Resolution ◽

Tryptophan Metabolites ◽

Q Exactive ◽

High Resolution Metabolomics ◽

Brain Tissues

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Effects of neuroactive metabolites of the tryptophan pathway on working memory and cortical thickness in schizophrenia

Translational Psychiatry ◽

10.1038/s41398-021-01311-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Junchao Huang ◽

Jinghui Tong ◽

Ping Zhang ◽

Yanfang Zhou ◽

Yimin Cui ◽

...

Keyword(s):

Working Memory ◽

Cognitive Impairment ◽

Cortical Thickness ◽

Serum Levels ◽

Healthy Controls ◽

Tryptophan Pathway ◽

Liquid Chromatography Tandem Mass ◽

Therapeutic Development ◽

Tryptophan Metabolites ◽

Insight Into

AbstractA number of tryptophan metabolites known to be neuroactive have been examined for their potential associations with cognitive deficits in schizophrenia. Among these metabolites, kynurenic acid (KYNA), 5-hydroxyindole (5-HI), and quinolinic acid (QUIN) are documented in their diverse effects on α-7 nicotinic acetylcholine receptor (α7nAChR) and/or N-methyl-D-aspartate receptor (NMDAR), two of the receptor types thought to contribute to cognitive impairment in schizophrenia. In this study, serum levels of KYNA, 5-HI, and QUIN were measured in 195 patients with schizophrenia and in 70 healthy controls using liquid chromatography-tandem mass spectrometry; cognitive performance in MATRICS Consensus Cognitive Battery and cortical thickness measured by magnetic resonance imaging were obtained. Patients with schizophrenia had significantly lower serum KYNA (p < 0.001) and QUIN (p = 0.02) levels, and increased 5-HI/KYNA (p < 0.001) and QUIN/KYNA ratios (p < 0.001) compared with healthy controls. Multiple linear regression showed that working memory was positively correlated with serum 5-HI levels (t = 2.10, p = 0.04), but inversely correlated with KYNA concentrations (t = −2.01, p = 0.05) in patients. Patients with high 5-HI and low KYNA had better working memory than other subgroups (p = 0.01). Higher 5-HI levels were associated with thicker left lateral orbitofrontal cortex (t = 3.71, p = 2.94 × 10−4) in patients. The different effects of 5-HI and KYNA on working memory may appear consistent with their opposite receptor level mechanisms. Our findings appear to provide a new insight into the dynamic roles of tryptophan pathway metabolites on cognition, which may benefit novel therapeutic development that targets cognitive impairment in schizophrenia.

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Chicken-eaters and pork-eaters have different gut microbiota and tryptophan metabolites

Scientific Reports ◽

10.1038/s41598-021-91429-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jie Shi ◽

Di Zhao ◽

Fan Zhao ◽

Chong Wang ◽

Galia Zamaratskaia ◽

...

Keyword(s):

Fatty Acids ◽

Gut Microbiota ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Branched Chain Fatty Acids ◽

Tryptophan Metabolites ◽

Branched Chain ◽

Spearman’S Correlation ◽

Gut Microbiota Composition ◽

Chain Fatty Acids

AbstractThis study was aimed to evaluate the differences in the composition of gut microbiota, tryptophan metabolites and short-chain fatty acids in feces between volunteers who frequently ate chicken and who frequently ate pork. Twenty male chicken-eaters and 20 male pork-eaters of 18 and 30 years old were recruited to collect feces samples for analyses of gut microbiota composition, short-chain fatty acids and tryptophan metabolites. Chicken-eaters had more diverse gut microbiota and higher abundance of Prevotella 9, Dialister, Faecalibacterium, Megamonas, and Prevotella 2. However, pork-eaters had higher relative abundance of Bacteroides, Faecalibacterium, Roseburia, Dialister, and Ruminococcus 2. In addition, chicken-eaters had high contents of skatole and indole in feces than pork-eaters, as well as higher contents of total short chain fatty acids, in particular for acetic acid, propionic acid, and branched chain fatty acids. The Spearman’s correlation analysis revealed that the abundance of Prevotella 2 and Prevotella 9 was positively correlated with levels of fecal skatole, indole and short-chain fatty acids. Thus, intake of chicken diet may increase the risk of skatole- and indole-induced diseases by altering gut microbiota.

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Lack of Skeletal Muscle Serotonin Impairs Physical Performance

International Journal of Tryptophan Research ◽

10.1177/11786469211003109 ◽

2021 ◽

Vol 14 ◽

pp. 117864692110031

Author(s):

Marion Falabrègue ◽

Anne-Claire Boschat ◽

Romain Jouffroy ◽

Marieke Derquennes ◽

Haidar Djemai ◽

...

Keyword(s):

Skeletal Muscle ◽

Endurance Training ◽

Physical Performance ◽

Depressive Disorders ◽

Tryptophan Metabolism ◽

Long Distance ◽

Positive Effects ◽

Tryptophan Metabolites ◽

The Brain ◽

Deficient Mice

Low levels of the neurotransmitter serotonin have been associated with the onset of depression. While traditional treatments include antidepressants, physical exercise has emerged as an alternative for patients with depressive disorders. Yet there remains the fundamental question of how exercise is sensed by the brain. The existence of a muscle–brain endocrine loop has been proposed: according to this scenario, exercise modulates metabolization of tryptophan into kynurenine within skeletal muscle, which in turn affects the brain, enhancing resistance to depression. But the breakdown of tryptophan into kynurenine during exercise may also alter serotonin synthesis and help limit depression. In this study, we investigated whether peripheral serotonin might play a role in muscle–brain communication permitting adaptation for endurance training. We first quantified tryptophan metabolites in the blood of 4 trained athletes before and after a long-distance trail race and correlated changes in tryptophan metabolism with physical performance. In parallel, to assess exercise capacity and endurance in trained control and peripheral serotonin–deficient mice, we used a treadmill incremental test. Peripheral serotonin–deficient mice exhibited a significant drop in physical performance despite endurance training. Brain levels of tryptophan metabolites were similar in wild-type and peripheral serotonin–deficient animals, and no products of muscle-induced tryptophan metabolism were found in the plasma or brains of peripheral serotonin–deficient mice. But mass spectrometric analyses revealed a significant decrease in levels of 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in both the soleus and plantaris muscles, demonstrating that metabolization of tryptophan into serotonin in muscles is essential for adaptation to endurance training. In light of these findings, the breakdown of tryptophan into peripheral but not brain serotonin appears to be the rate-limiting step for muscle adaptation to endurance training. The data suggest that there is a peripheral mechanism responsible for the positive effects of exercise, and that muscles are secretory organs with autocrine-paracrine roles in which serotonin has a local effect.

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Exploitation of the IDO Pathway in the Therapy of Rheumatoid Arthritis

International Journal of Tryptophan Research ◽

10.4137/ijtr.s11737 ◽

2013 ◽

Vol 6s1 ◽

pp. IJTR.S11737 ◽

Cited By ~ 5

Author(s):

Richard O. Williams

Keyword(s):

Rheumatoid Arthritis ◽

Anthranilic Acid ◽

Kynurenine Pathway ◽

Gene Encoding ◽

Rate Limiting Step ◽

Tryptophan Metabolites ◽

Synthetic Derivative ◽

Rate Limiting ◽

Kinetics Of ◽

Draining Lymph Nodes

Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting step along the kynurenine pathway and is thought to play a key role in immune homeostasis through depletion of tryptophan and accumulation of kynurenines. In this review we summarize recent research into the possibility of harnessing the IDO pathway for the therapy of rheumatoid arthritis. Inhibition of IDO activity, or knockout of the gene encoding IDO, was shown to cause an increase in the severity of collagen-induced arthritis, an animal model of rheumatoid arthritis. The increased severity of disease was associated with elevated numbers of pathogenic Th1 and Th17 cells in the joints and draining lymph nodes. In another study, analysis of the kinetics of expression of downstream kynurenine pathway enzymes during the course of arthritis revealed a potential role for tryptophan metabolites in resolution of arthritis. Furthermore, the therapeutic administration of L-kynurenine or [3,4-dimethoxycinnamonyl]-anthranilic acid (a synthetic derivative of 3-hydroxy-anthranilic acid) significantly reduced both clinical and histological progression of experimental arthritis. These findings raise the possibility of exploiting the IDO pathway for the therapy of autoimmune disease.

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