Serum Tryptophan Concentrations Research Articles

5-hydroxytryphophan mitigates ergot alkaloid-induced suppression of serotonin and feed intake in cattle.

The impact of ergot toxicosis on livestock industries is detrimental and treatments are needed in many countries. The objective of this study was to evaluate the effects of acute exposure to ergot alkaloids and 5-hydroxytryptophan (5-HTP) supplementation on feed intake, serotonin metabolism, and blood metabolites in cattle. Eight Holstein steers (538 ± 18kg) fitted with ruminal cannulas were used in a replicated 4 × 4 Latin Square design experiment with a 2 × 2 factorial treatment structure. The treatments were the combination of 0 (E-) or 15 µg ergovaline/kg BW (E+) and 0 (5HTP-) or 0.5mg of 5-hydroxy-l-tryptophan/kg BW (5HTP+) administered daily for 6 d. Toxic endophyte-infected tall fescue seed was used to supply the daily dose of ergovaline. Endophyte-free seed was used to equalize seed intake between treatments. Ground seed was placed into the rumen immediately before feeding. The 5-HTP was dissolved in water and infused into the abomasum via the reticulo-omasal orifice. Blood was collected from a jugular vein catheter at 0, 1, 2, 4, 8, and 24h after treatment administration. Ergovaline without 5-HTP (E+/5HTP-) decreased dry matter intake (DMI) in comparison to steers without ergovaline and 5-HTP (E-/5HTP-). However, 5-HTP infusion in association with ergovaline (E+/5HTP+) normalized the DMI. Although E + did not affect (P > 0.05) the area under the curve (AUC) of serum 5-HTP, 5-hydroxyindoleacetic acid, tryptophan, and kynurenine, serum and plasma serotonin concentrations were decreased (P < 0.05). The infusion of 5-HTP increased (P < 0.05) the AUC of serum 5-HTP, serum and plasma serotonin, and serum 5-hydroxyindoleacetic acid. In conclusion, acute exposure to ergot alkaloids reduced DMI and circulating serotonin in cattle but 5-HTP administration showed potential to normalize both circulating serotonin and feed intake.

Chronic Inflammatory Enteropathy and Low-Grade Intestinal T-Cell Lymphoma Are Associated with Altered Microbial Tryptophan Catabolism in Cats.

Chronic inflammatory enteropathy (CIE) and low-grade intestinal T-cell lymphoma (LGITL) are common chronic enteropathies (CE) in cats. Enteric microbiota dysbiosis is implicated in the pathogenesis of CE; however, the mechanisms of host-microbiome interactions are poorly understood in cats. Microbial indole catabolites of tryptophan (MICT) are gut bacterial catabolites of tryptophan that are hypothesized to regulate intestinal inflammation and mucosal barrier function. MICTs are decreased in the sera of humans with inflammatory bowel disease and previous studies identified altered tryptophan metabolism in cats with CE. We sought to determine whether MICTs were decreased in cats with CE using archived serum samples from cats with CIE (n = 44) or LGITL (n = 31) and healthy controls (n = 26). Quantitative LC-MS/MS was used to measure serum concentrations of tryptophan, its endogenous catabolites (kynurenine, kynurenate, serotonin) and MICTs (indolepyruvate, indolealdehyde, indoleacrylate, indoleacetamide, indoleacetate, indolelactate, indolepropionate, tryptamine). Serum concentrations of tryptophan, indolepropionate, indoleacrylate, indolealdehyde, indolepyruvate, indolelactate were significantly decreased in the CIE and LGITL groups compared to those in healthy controls. Indolelactate concentrations were significantly lower in cats with LGITL compared to CIE (p = 0.006). Significant correlations were detected among serum MICTs and cobalamin, folate, fPLI, and fTLI. Our findings suggest that MICTs are promising biomarkers to investigate the role of gut bacteria in the pathobiology of chronic enteropathies in cats.

A systematic review and meta-analysis of the kynurenine pathway of tryptophan metabolism in rheumatic diseases.

https://www.crd.york.ac.uk/prospero, identifier CRD CRD42023443718.

Treatment of ankylosing spondylitis with TNFα inhibitors does not affect serum levels of tryptophan metabolites.

The imbalance between the kynurenine and serotonin pathways can have serious consequences, e.g., depression. One of the factors leading to the imbalance between the pathways of tryptophan metabolism is inflammation. The aim of our study was to assess the impact of treatment with tumor necrosis factor-alpha (TNFα)-inhibitors on tryptophan metabolism in patients with ankylosing spondylitis (AS). Forty patients with AS (twenty-eight males, twelve females; mean age 40 ± 11years), qualified to receive anti-TNF-α treatment, were prospectively assessed. As a control group, 20 healthy volunteers (7 males and 13 females, mean age 38 ± 5years) were recruited from the general population. Patients underwent full clinical and biochemical assessment before and after 6months of therapy. Disease activity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The presence of depressive disorders was assessed with Beck's Depression Inventory (BDI) scale. Serum concentrations of tryptophan, serotonin, kynurenine, and quinolinic acid were measured. The predominance of the kynurenine pathway in AS patients (compared to the control group) was demonstrated (p < 0.001). Surprisingly, no significant changes in serum levels of tryptophan and its metabolites in AS patients after treatment were found, despite clinical improvement. Moreover, the components of tryptophan metabolism did not correlate significantly with the clinical activity of AS, depression nor laboratory inflammatory markers. Probably some other factors influence the pathways of tryptophan metabolism in patients with ankylosing spondylitis.

The serum kynurenine pathway metabolic profile is associated with overweight and obesity in multiple sclerosis.

Overweight and obesity increase multiple sclerosis (MS) susceptibility, disease severity, and disability progression. Kynurenine pathway (KP) dysregulation is present in overweight and obesity, and in MS. Since the effect of overweight and obesity on KP dysregulation in persons with MS (pwMS) remains to be established, this study primarily aims to explore the effect of overweight and obesity on the serum KP metabolic profile in pwMS. This cross-sectional study represents a secondary analysis of a randomized clinical trial at Valens rehabilitation clinic, Switzerland. Registration was performed on 22 April 2020 at clinicaltrials.gov (NCT04356248, https://clinicaltrials.gov/ct2/show/NCT04356248). The first participant was enrolled on 13 July 2020. Based on body mass index (BMI), 106 MS inpatients (Expanded Disability Status Scale (EDSS) score ≤ 6.5) were dichotomised to a lean group (LG, BMI < 25kg/m2), and an overweight/obese group (OG, BMI ≥ 25kg/m2). Targeted metabolomics (LC-MS/MS) was performed to determine serum concentrations of tryptophan (TRP), KP downstream metabolites, and neopterin (Neopt). Correlations between BMI, kynurenine-to-TRP ratio (KTR), and serum concentrations of TRP, KP downstream metabolites, and Neopt were calculated. ANCOVA was used to determine differences in KTR, and serum concentrations of TRP, KP downstream metabolites and Neopt between OG and LG, and across MS phenotypes. Higher BMI correlated with higher KTR (r=0.425, p <0.001) and serum concentrations of most KP downstream metabolites, but not with EDSS score. Higher KTR (r=0.470, p < .001) and serum concentrations of most KP downstream metabolites correlated with a higher serum concentration of Neopt. The OG (n=44, 59% female, 51.68 (9.98) years, EDSS: 4.71 (1.37)) revealed higher KTR (0.026 (0.007) vs. 0.022 (0.006), p=.001) and serum concentrations of most KP downstream metabolites than the LG (n=62, 71% female, 48.37 (9.63) years, EDSS: 4.60 (1.29)). KP metabolic profiles did not differ between MS phenotypes. Overweight and obesity are associated with a systemic elevation of KP metabolic flux and an accumulation of most KP downstream metabolites in pwMS. Further research is needed to clarify if KP involvement serves as a mechanism linking overweight and obesity with symptom expression, disease severity, and disability progression in pwMS.

Measurement of kynurenine pathway metabolites by tandem mass spectrometry

ObjectivesRecent studies have shown that derangements in kynurenine pathway metabolite levels are associated with various pathologies such as neurodegenerative diseases, schizophrenia, depression, bipolar disorder, rheumatoid arthritis, and cancer. Therefore, reliable, accurate, fast, and multiplex measurement methods for kynurenines have become increasingly important. This study aimed to validate a new mass spectrometric method for analyzing tryptophan metabolites. MethodsA tandem mass spectrometric method, including protein precipitation and evaporation steps, was developed to measure serum levels of tryptophan, kynurenine, kynurenic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid. Samples were separated using a Phenomenex Luna C18 reversed-phase column. The kynurenine pathway metabolites were detected by tandem mass spectrometry. The developed method was validated according to Clinical & Laboratory Standards Institute (CLSI) guidelines and applied to hemodialysis samples. ResultsThe developed method was linear at the concentrations of 48.8 – 25,000, 0.98 – 500, 1.2–5000, 1.2–5000, and 0.98–250 ng/mL for tryptophan, kynurenic acid, kynurenine, 3-hydroxyanthranilic acid, and 3-hydroxykynurenine, respectively. The imprecisions were less than 12 %. The median serum concentrations of tryptophan, kynurenine, kynurenic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid were 10530, 1100, 218, 17.6, and 25.4 ng/mL in pre-dialysis blood samples, respectively. They were 4560, 664, 135, 7.4, and 12.8 ng/mL in post-dialysis blood samples, respectively. ConclusionsA fast, simple, cost-effective, accurate, robust, and validated tandem mass spectrometric method was developed, and the method was successfully used for the quantitation of kynurenine pathway metabolite concentrations in hemodialysis patients.

Normative Data on Serum and Plasma Tryptophan and Kynurenine Concentrations from 8089 Individuals Across 120 Studies: A Systematic Review and Meta-Analysis.

In this systematic review and meta-analysis, a normative dataset is generated from the published literature on the kynurenine pathway in control participants extracted from case-control and methodological validation studies. Study characteristics were mapped, and studies were evaluated in terms of analytical rigour and methodological validation. Meta-analyses of variance between types of instruments, sample matrices and metabolites were conducted. Regression analyses were applied to determine the relationship between metabolite, sample matrix, biological sex, participant age and study age. The grand mean concentrations of tryptophan in the serum and plasma were 60.52 ± 15.38 μM and 51.45 ± 10.47 μM, respectively. The grand mean concentrations of kynurenine in the serum and plasma were 1.96 ± 0.51 μM and 1.82 ± 0.54 μM, respectively. Regional differences in metabolite concentrations were observed across America, Asia, Australia, Europe and the Middle East. Of the total variance within the data, mode of detection (MOD) accounted for up to 2.96%, sample matrix up to 3.23%, and their interaction explained up to 1.53%; the latter of which was determined to be negligible. This review was intended to inform future empirical research and method development studies and successfully synthesised pilot data. The pilot data reported in this study will inform future precision medicine initiatives aimed at targeting the kynurenine pathway by improving the availability and quality of normative data.

KXS Balances the Tryptophan Metabolism in Mild to Moderate Depressed Patients and Chronic Restraint Stress Induced Depressive Rats.

Tryptophan metabolism is involved in the etiology and exacerbation of depressive disorders. Kai-Xin-San (KXS), a traditional Chinese medicine formula, has been widely used to treat depression and modulate serotonin simultaneously, but how it regulates depressive-like behavior by shifting the balance of the tryptophan-serotonin metabolism and kynurenine pathway remains vague. Ten participants with mild to moderate depression treated with KXS (KXS preparation) were analyzed in this study. Depression rating scale score and the concentration of serum tryptophan, 5-hydroxytryptophan and kynurenine was measured at baseline and the endpoint of KXS treatment. To explore the specific regulatory mechanism of KXS in tryptophan metabolism, the chronic restraint stress (CRS) was used to induce depressive-like syndrome in rats and the hippocampus level of tryptophan, 5-hydroxytryptophan, kynurenine with downstream metabolites (kynurenic acid, quinolinic acid) and key enzymes (indoleamine 2,3-dioxygenase, kynurenine 3-monooxygenase, kynurenine aminotransferase) were analyzed by liquid chromatography-electros pray ionization tandem mass spectrometry, high performance liquid chromatography and enzyme-linked immunosorbent assay respectively. KXS significantly decreased depression rating scale scores and increased the serum tryptophan and kynurenine concentration in depressive patients compared to baseline. Also, it alleviated the depressive behavior in CRS rats obviously. Comparing with CRS group, KXS increased tryptophan, 5-hydroxytryptophan, kynurenine level in rat hippocampus. Furthermore, in kynurenine pathway, KXS decreased the expression of indoleamine 2,3-dioxygenase, increased kynurenic acid by upregulating the expression of kynurenine aminotransferase while decreased quinolinic acid level in hippocampus, which suggested that KXS more favored improving serotonin pathway, and neuroprotective kynurenic acid branch in the tryptophan metabolism. This is the first tryptophan metabolomic study of patients with depression undergoing KXS treatment. Combining these clinical results with CRS induced rat model studies, it verified that KXS achieves an excellent antidepressant effect and balances tryptophan-kynurenine metabolic pathways by regulating some key metabolic products and enzymes.

Obez hastalarda serum leptin ve triptofan düzeylerinin depresyon ve anksiyete ile ilişkisi var mı?

Objectives: Depression and anxiety are common conditions in obese patients. Leptin plays a role in obesity, the role of tryptophan in obesity has been investigated frequently in current studies. The aim of this study is to evaluate whether serum leptin and triptophan levels are related to depression and anxiety in obesity patients. Methods: This is a descriptive and cross-sectional study in which the data of 88 patients aged 18 years and over, BMI 25 kg/m2 and above, who applied to the Family Medicine outpatient clinic between 01.07.2019 and 31.12.2019, were examined. Sociodemographic data form, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) were completed by all patients included in the study. Results: There was no significant relationship between BMI and leptin, BMI and tryptophan levels. A positive correlation was found between tryptophan and weight, waist circumference and systolic blood pressure (SBP). Tryptophan was also significantly higher in smokers and those with a history of psychiatric treatment. Tryptophan levels in men were found to be significantly higher than in women. Serum tryptophan concentration of the patients was positively correlated with weight, waist circumference and SBP. Tryptophan level was found significantly higher in men than in women. Tryptophan was also significantly higher in smokers and those with a history of psychiatric treatment. There was no significant relationship between BDI, BAI and leptin and tryptophan levels. Conclusion: The significant relationships between serum tryptophan level and weight, waist circumference and SBP may be useful in the management, follow-up and treatment of obese patients.

Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial

Fatigue is highly prevalent among patients with inflammatory bowel disease (IBD), and only limited treatment options are available. Based on the hypothetical link between low serum tryptophan concentrations and fatigue, we determined the effect of 5-hydroxytryptophan supplementation on fatigue in patients with inactive IBD. A multicenter randomized controlled trial was performed at 13 Belgian hospitals, including 166 patients with IBD in remission but experiencing fatigue, defined by a fatigue visual analog scale (fVAS) score of ≥5. Patients were treated in a crossover manner with 100 mg oral 5-hydroxytryptophan or placebo twice daily for 2 consecutive periods of 8 weeks. The primary end point was the proportion of patients reaching a ≥20% reduction in fVAS after 8 weeks of intervention. Secondary outcomes included changes in serum tryptophan metabolites, Functional Assessment of Chronic Illness Therapy Fatigue scale, and scores for depression, anxiety, and stress. The effect of the intervention on the outcomes was evaluated by linear mixed modeling. During 5-hydroxytryptophan treatment, a significant increase in serum 5-hydroxytryptophan (estimated mean difference, 52.66 ng/mL; 95% confidence interval [CI], 39.34-65.98 ng/mL; P < .001) and serotonin (3.0 ng/mL; 95 CI, 1.97-4.03 ng/mL; P < .001) levels was observed compared with placebo. The proportion of patients reaching ≥20% reduction in fVAS was similar in placebo- (37.6%) and 5-hydroxytryptophan (35.6%)-treated patients (P= .830). The fVAS reduction (-0.18; 95% CI,-0.81 to 0.46; P= .581) and Functional Assessment of Chronic Illness Therapy Fatigue scale increase (0.68; 95% CI,-2.37 to 3.73; P= .660) were both comparable between 5-hydroxytryptophan and placebo treatment as well as changes in depression, anxiety, and stress scores. Despite a significant increase in serum 5-hydroxytryptophan and serotonin levels, oral 5-hydroxytryptophan did not modulate IBD-related fatigue better than placebo. (Trial Registration: Belgian Federal Agency for Medication and Health Products, EudraCT number: 2017-005059-10 and ClinicalTrials.gov: NCT03574948, https://clinicaltrials.gov/ct2/show/NCT03574948.).

Tryptophan metabolism in bipolar disorder

IntroductionImmune mediated inflammatory processes are involved in the aetiopathogenesis of bipolar disorder (BD) and weight associated comorbidities. Tryptophan breakdown via indoleamine 2,3-dioxygenase-1 (IDO-1) along the kynurenine axis concomitant with a pro-inflammatory state was found more active in BD but also associated with overweight/obesity.ObjectivesAims of our study were to investigate 1.) the tryptophan metabolism in BD compared to mentally healthy controls, 2.) differences in weight classes, 3.) in a longitudinal setting, dependent on the incidence of BD episodes and euthymia.MethodsAt the Medical University Graz anthropometric and clinical data as well as peripheral tryptophan and kynurenine were assessed in serum samples of 226 individuals with BD and 142 controls. For 75 individuals with BD a longitudinal assessment with three samples was performed. Serum concentrations of tryptophan and kynurenine were determined by reverse-phase high-performance liquid chromatography. The kynurenine/tryptophan was used as a proxy for IDO-1 activity.Resultsshowed a higher kynurenine/tryptophan ratio in BD compared to controls and in overweight compared to normal weight persons. Levels remained stable over time. In the longitudinal course, no differences were found between individuals who were constantly euthymic or not as well who had an illness episode or none.ConclusionsFindings indicate that IDO-1 activity might constitute more a trait and not a state marker of BD. Accelerated tryptophan breakdown along the kynurenine axis may be further facilitated by overweight. This may increase the risk of accumulation of neurotoxic metabolites which impacts BD symptomatology, cognition, and somatic comorbidities.DisclosureNo significant relationships.

The Kynurenine Pathway in Obese Middle-Aged Women with Normoglycemia and Type 2 Diabetes.

We examined the relationships of tryptophan (Trp) and the metabolites of the kynurenine pathway (KP) to the occurrence of type 2 diabetes (T2D) and metabolic risk factors in obese middle-aged women. The study included 128 obese women divided into two subgroups: a normoglycemic group (NG, n = 65) and a T2D group (n = 63). The concentrations of serum tryptophan (Trp), kynurenine (Kyn), 3-hydroxykynurenine (3HKyn), quinolinic acid (QA), and kynurenic acid (Kyna) were analyzed using ultra-high-performance liquid chromatography coupled with electrospray ionization/triple quadrupole mass spectrometry. Blood biochemical parameters and anthropometric parameters were measured. The women with T2D had significantly higher Trp, Kyna, Kyna/QA ratio, and Kyna/3HKyn ratio values than the NG women. Logistic regression analysis showed that the concentrations of Trp and Kyna and the values of the Kyna/3HKyn ratio were most strongly associated with T2D occurrence, even after controlling for confounding factors. The model with Trp level and Kyna/3HKyn ratio accounted for 20% of the variation in the presence of T2D. We also showed a different pattern of correlations between kynurenines and metabolic factors in the NG and T2D women, which was mostly reflected in the stronger relationship between BMI and KP metabolites in the NG obese women. An increase in Trp and Kyna levels with an accompanying increase in Kyna/3HKyn ratio value is associated with the occurrence of T2D in obese middle-aged women.

Beneficial Effects of a Low-Glycemic Diet on Serum Metabolites and Gut Microbiota in Obese Women With Prevotella and Bacteriodes Enterotypes: A Randomized Clinical Trial.

Generalized healthy eating patterns may not benefit everyone due to different genetics and enterotypes. We aimed to compare the effects of a low-glycemic diet representing the Korean traditional balanced diet (Low-GID) and westernized diet as a control diet (CD) on anthropometry, serum metabolites, and fecal bacteria in a randomized clinical trial according to enterotypes. We recruited 52 obese women aged 30–50 years, and they consumed Low-GID and CD meals for 1 month, with a 1-month washout period, in a crossover randomized clinical trial. The Low-GID was mainly composed of whole grains with fish, vegetables, seaweeds, and perilla oil, whereas CD contained refined rice, bread, noodles, meats, and processed foods. Serum lipid profiles, metabolomics, serum short-chain fatty acids, and fecal bacteria were analyzed. The important variables influenced by Low-GID and CD were determined by SHAP value in the XGBoost algorithm according to Bacteroides (ET-B) and Prevotella (ET-P). Low-GID and CD interventions did not change the enterotypes, but they modified serum metabolites and some fecal bacterial species differently according to enterotypes. The 10-fold cross-validation of the XGBoost classifier in the ET-P and ET-B clusters was 0.91 ± 0.04 and 0.8 ± 0.07, respectively. In the ET-P cluster, serum L-homocysteine, glutamate, leucine concentrations, and muscle mass were higher in the CD group than in the Low-GID group, whereas serum 3-hydroxybutyric acid concentration was significantly higher in the Low-GID group than in the CD group (p < 0.05). In fecal bacteria, Gemmiger formicilis, Collinsella aerofaciens, and Escherichia coli were higher in the CD group than in the Low-GID group. In the ET-B cohort, serum tryptophan and total cholesterol concentrations were higher in the CD group than in the Low-GID group, whereas serum glutathione and 3-hydroxybutyric acid concentrations were significantly higher in the Low-GID group than in the CD group (p < 0.05). However, Bifidobacterium longum was higher in CD than Low-GID in the ET-B cluster, but serum butyric acid levels were higher in the Low-GID than in the CD group. In conclusion, Low-GID can be recommended in obese women with both ET-P and ET-B enterotypes, although its efficacy was more effective in ET-P.Clinical Trial Registration[https://cris.nih.go.kr/cris/search/detailSearch.do/17398], identifier [KCT0005340].

Kynurenine pathway of tryptophan metabolism in patients with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autoinflammatory syndrome characterized by recurrent episodes of fever and aseptic polyserositis. Subclinical inflammation generates a hidden threat to the development of FMF complications such as amyloidosis in attack-free intervals. The kynurenine pathway (KP) has been considered an important player in inflammation and immune response. The study was aimed to measure serum levels of KP metabolites in patients with FMF in the attack-free period. A total of 161 participants were recruited from the rheumatology department in this single-centre, case-control study. Participants meeting the eligibility criteria were divided into healthy controls (n = 80) and FMF (n = 81). The laboratory data were obtained from the electronic registration database. Serum tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxyanthranilic acid, 3-hydroxykynurenine (3HK), and quinolinic acid (QUIN) concentrations were measured with tandem mass spectrometry. Laboratory findings of FMF patients and healthy controls subjects were compared and evaluated. Serum TRP and KYNA levels were significantly decreased in both FMF groups compared to the control group, while the levels of KYN, QUIN, 3HK, the KYN/TRP ratio, and red cell distribution width were higher. TRP degradation by the KP is increased in patients with FMF. KP metabolites can be useful in demonstrating subclinical inflammation.

Correlation between serotonin and tryptophan serum concentrations in shelter dogs undergoing a stressful procedure

Correlation between serotonin and tryptophan serum concentrations in shelter dogs undergoing a stressful procedure

Tryptophan, Kynurenine and Kynurenic Acid Concentrations in Milk and Serum of Dairy Cows with Prototheca Mastitis.

Simple SummaryBovine mastitis continues to be a leading cause of heavy economic losses in the dairy industry worldwide. Among a broad spectrum of infectious agents implicated in this pathology are unicellular, achlorophyllous microalgae of the genus Prototheca. The prevalence of mastitis due to Prototheca algae is currently increasing. The aim of this work was to explore a possible association of the kynurenine pathway of tryptophan metabolism with Prototheca mastitis. The authors were eager to know whether metabolites of tryptophan degradation can be used as markers of the protothecal bovine mastitis. Both tryptophan and its metabolite kynurenine occurred at a significantly lower level in the milk of cows with mastitis compared to healthy animals. Whereas the activity of indoleamine 2,3-dioxygenase, a key enzyme of tryptophan catabolism, was significantly higher in milk of mastitic cows compared to control animals. It was thus concluded that low values of tryptophan and kynurenine concentrations or elevated indoleamine 2,3-dioxygenase activity in milk samples can be used as markers of mastitis due to Prototheca spp.The aim of this work was to investigate serum and milk levels of tryptophan (TRP), kynurenine (KYN), and kynurenic acid (KYNA), as well as the activity of indoleamine 2,3-dioxygenase (IDO) in cows with mastitis due to Prototheca algae. The study was prompted by previous research showing a link between the KYN pathway of TRP metabolism and bovine mastitis of bacterial etiology. The study was carried out over a 2-year period (2018–2019) and included quarter milk and serum samples collected from six dairy herds in Poland. The samples were obtained from healthy cows and cows with Prototheca mastitis of either clinical and subclinical manifestation, as determined upon direct measurement of the somatic cell count or indirectly by performing a California Mastitis Test on suspected quarters. Both TRP and KYN concentrations were significantly lower in milk of mastitic cows compared to healthy animals (0.8 vs. 8.72 µM, p = 0.001; 0.07 vs. 0.32 µM, p = 0.001, respectively). The difference in TRP and KYN concentrations in the sera of the two animal groups was much less pronounced (25.55 vs. 27.57 µM, 3.03 vs. 3.56 nM, respectively). The concentration of KYNA was almost at the same level in milk (1.73 vs. 1.70 nM) and in serum (80.47 vs. 75.48 nM) of both mastitic and healthy cows. The data showed that the level of TRP and its metabolites in serum was conspicuously higher compared to milk in all cows under the study. The activity of IDO was significantly higher in milk of cows with Prototheca mastitis compared to healthy animals (71.4 vs. 40.86, p < 0.05), while in serum it was pretty much the same (135.94 vs. 124.98, p > 0.05). The IDO activity differed significantly between serum and milk both for mastitic (135.94 vs. 71.4, p < 0.05) and healthy cows (124.98 vs. 40.86, p < 0.001). In conclusion, low values of TRP and KYN concentrations or elevated IDO activity in milk samples might be used as markers of mastitis due to infectious causes, including Prototheca spp.

Quantifying Serum Total Lipids and Tryptophan Concentrations by Raman Spectroscopy During Standardized Obstacle Course in Horses

Raman spectroscopy is an inelastic light-scattering phenomenon that provides vibrational spectrum that contains information relative to chemical bonds and symmetry of a specific molecule, allowing the quali-quantitative simultaneous determination of several components in the biological fluids. Raman spectroscopy measurement returns a spectrum over a wavenumber range constituted by several bands representing biomarkers according to investigated biological matrices. In literature, it has been reported that at the frequencies inside the (1,300–1,360) cm−1 total lipids, and tryptophan have been identified. On the basis of that, the aim of the present study was to compare the serum concentration of total lipids and tryptophan in horses subjected to a standardized obstacle course, in comparison with the data obtained in the (1,300–1,360) cm−1 band. At this purpose, five clinically healthy and regularly trained Italian Saddle horses aged between 8, and 10 years old performed with the same rider an obstacle course of 350 m/min with twelve 1.30 m high jumps preceded by warm-up. Blood samples were collected by means of jugular venipuncture into a vacutainer tubes with clot activator at rest, after the exercise, and 30 minutes after the end of exercise. A high correlation was observed between the area of total lipids and tryptophan in the (1,300–1,360) cm−1 band and their serum concentrations in all experimental conditions. Our preliminary results give a hint to study the exact correspondence between the area that identify these parameters in Raman spectrum and their serum concentration in athletic horses.

Serum profiles of tryptophan-kynurenine pathway metabolites in psoriasis

Aim: Chronic inflammation is closely associated with tryptophan (TRP)-kynurenine (KYN) metabolic pathway. However, TRP-KYN pathway has not been fully elucidated in psoriasis, a systemic inflammatory disease with skin lesions and extracutaneous manifestations. Herein, we studied comprehensively serum profiles of TRP-KYN pathway metabolites in psoriatic patients (PSOs) to clarify the involvement of this pathway in the pathophysiology of psoriasis and to evaluate serum biomarkers reflecting systemic inflammation in PSOs. Methods: The concentrations of main TRP metabolites, TRP, KYN, 3-hydroxykynurenine (3HK), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), and anthranilic acid (AA), were determined by high-performance liquid chromatography in the sera from 65 PSOs and 35 healthy controls (HCs). The levels of these metabolites and the ratios of metabolites were compared between these subjects. The correlations between these values and the psoriasis area severity index (PASI) scores were analyzed. Skin samples from PSOs and HCs were subjected to immunohistochemical staining for kynureninase. Cytokine concentrations were comprehensively measured in the same samples and the correlations between the cytokine levels and TRP-KYN pathway metabolite levels were examined. Results: Serum TRP, KYN, and KYNA concentrations were lower and the 3HAA concentrations were higher in PSOs than in HCs. The ratios of 3HK/KYN, 3HAA/3HK, and 3HK/AA were higher in PSOs than in HCs. The AA levels and the ratio of AA/KYN were weakly positively correlated, and TRP, KYNA, and 3HK levels and the ratios of KYNA/KYN and 3HAA/AA were weakly negatively correlated with the PASI scores. The AA, KYN, and KYNA levels were positively correlated with the interferon gamma-induced protein 10 (IP-10) concentrations. Kynureninase expression was enhanced in the epidermis, both involved and uninvolved skin. Conclusions: Serum profiles of TRP-KYN pathway metabolites differed between PSOs and HCs. TRP-KYN pathway-associated processes, including kynureninase activation, may be involved in the pathogenesis of psoriasis, and thus serve as targets for psoriasis therapy.

The Impact of Cardiovascular Rehabilitation on Psychophysiological Stress, Personality and Tryptophan Metabolism: A Randomized Pilot Feasibility Study.

Multicomponent cardiac rehabilitation (CR) is a secondary prevention strategy for cardiac patients to tackle stress and psychosocial wellbeing. However, there is a lack of data on its psychoneuroimmunological effects and of biomarkers to determine individual risk and to develop treatment strategies. We conducted a pilot randomized controlled trial (RCT) to investigate the feasibility of deriving psychophysiological stress markers in patients with cardiovascular diseases. Thirty individuals with cardiovascular disease (mean age 58.8 years; 23.3% female) were enrolled and randomized into three treatment groups: standard rehabilitation, yoga, or transcendental meditation (TM). Depression, anxiety, sleep, stress perception, personality functioning, hair cortisol, serum tryptophan, kynurenine and neopterin concentrations were estimated at baseline and after a four-week intervention. Hair cortisol levels decreased significantly after rehabilitation in all groups (F = 15.98, p < 0.001). In addition, personality functioning improved in all patients over time. Participants with impairments in personality functioning showed a positive correlation with baseline neopterin that did not remain significant after Bonferroni correction. Concentrations of serum tryptophan and its metabolite kynurenine did not change significantly. This pilot RCT provides preliminary evidence of multicomponent CR leading to stabilization of hair cortisol levels and improved psychophysiological wellbeing and personality functioning. Impairments in personality functioning were correlated with neopterin levels, which may impact the symptomatology and outcome.

Prospective study on the association between serum amino acid profiles and depressive symptoms among the Japanese working population

ObjectiveAccumulating evidence suggests that amino acids, particularly tryptophan and glutamate, play an important role in the pathology of depression, but prospective epidemiologic data on this issue is scarce. We examined the association between circulating amino acids and the risk of depressive symptoms in a Japanese working population.MethodsParticipants were 841 workers who were free from depressive symptoms and provided blood at baseline and completed 3-yr follow-up survey. 30 varieties of amino acid concentrations in serum were measured using liquid chromatography/mass spectrometry. Depressive symptoms were defined using the Center for Epidemiologic Studies Depression Scale. Logistic regression was used to calculate the odds ratios of depressive symptoms according to serum amino acids with adjustment for lifestyle factors.ResultsA total of 151 (18.0%) workers were newly identified as having depressive symptoms at the follow-up. Baseline tryptophan and glutamate concentrations in serum were not appreciably associated with the risk of depressive symptoms. Risk of depressive symptoms tended to increase with increasing arginine concentrations; the multivariable-adjusted odds ratio for the highest versus lowest tertile of serum arginine was 1.65 (95% confidence interval: 0.96–2.83; P for trend = 0.07). No clear association was found for other amino acids.ConclusionsResults of the present study do not support a significant role of circulating amino acids in the development of depressive symptoms among Japanese.