tryptophan metabolism
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Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 286
Author(s):  
Julia Lischka ◽  
Andrea Schanzer ◽  
Margot Baumgartner ◽  
Charlotte de Gier ◽  
Susanne Greber-Platzer ◽  
...  

The obesity epidemic has contributed to an escalating prevalence of metabolic diseases in children. Overnutrition leads to increased tryptophan uptake and availability. An association between the induction of the tryptophan catabolic pathway via indoleamine 2,3-dioxygenase (IDO) activity and obesity-related inflammation has been observed. This study aimed to investigate the impact of pediatric obesity on tryptophan metabolism and the potential relationship with metabolic disease. In this prospective cohort study, plasma kynurenine, tryptophan, and serotonin levels were measured by ELISA, and IDO activity was estimated by calculating the kynurenine/tryptophan ratio in a clinically characterized population with severe obesity (BMI ≥ 97th percentile) aged 9 to 19 (n = 125). IDO activity and its product kynurenine correlated with BMI z-score and body fat mass, whereas concentrations of serotonin, the alternative tryptophan metabolite, negatively correlated with these measures of adiposity. Kynurenine and tryptophan, but not serotonin levels, were associated with disturbed glucose metabolism. Tryptophan concentrations negatively correlated with adiponectin and were significantly higher in prediabetes and metabolically unhealthy obesity. In conclusion, BMI and body fat mass were associated with increased tryptophan catabolism via the kynurenine pathway and decreased serotonin production in children and adolescents with severe obesity. The resulting elevated kynurenine levels may contribute to metabolic disease in obesity.


2022 ◽  
Vol 8 ◽  
Author(s):  
Gaurav Tripathi ◽  
Sheetalnath Rooge ◽  
Manisha Yadav ◽  
Babu Mathew ◽  
Nupur Sharma ◽  
...  

Introduction: With the advent of direct-acting antiviral (DAA) therapy for HCV, the cure is achieved at similar rates among HIV–HCV coinfected patients as in HCV mono-infected patients. The present study evaluates host plasma metabolites as putative indicators in predicting the treatment response in baseline HIV–HCV patients.Methods: Non-cirrhotic HIV–HCV (N = 43) coinfected patients were treated with sofosbuvir and daclatasvir for 12 weeks. Plasma metabolite profiling of pre- and post-therapy was analyzed in 20/43 patients. Of the 20 selected, 10 (50%) attained the sustained viral response [(SVR) (responders)] as defined by the absence of HCV RNA at 12 weeks after the treatment, and 10 (50%) did not attain the cure for HCV (nonresponders).Results: A total of 563 features were annotated (metabolomic/spectral databases). Before therapy, 39 metabolites differentiated (FC ±1.5, p < 0.05) nonresponders from responders. Of these, 20 upregulated and 19 downregulated were associated with tryptophan metabolism, nicotinamide metabolism, and others. Post therapy, 62 plasma metabolites (12 upregulated and 50 downregulated, FC±1.5, p < 0.05) differentiated nonresponders from responders and highlighted a significant increase in the steroid and histidine metabolism and significant decrease in tryptophan metabolism and ascorbate and pyruvate metabolism in the nonresponders. Based on random forest and multivariate linear regression analysis, the baseline level of N-acetylspermidine (FC > 2, AUC = 0.940, Bfactor = −0.267) and 2-acetolactate (FC > 2, AUC = 0.880, Bfactor = −0.713) significantly differentiated between nonresponders from responders in HIV–HCV coinfected patients and was able to predict the failure of treatment response.Conclusion: Increased baseline levels of N-acetylspermidine and 2-acetolactate levels are associated with the likeliness of failure to attain the cure for HCV in HIV–HCV coinfected patients.


Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 443
Author(s):  
Yang Ai ◽  
Sang Luo ◽  
Ben Wang ◽  
Shuai Xiao ◽  
Yefu Wang

TDO2 is a key enzyme in the kynurenine metabolic pathway, which is the most important pathway of tryptophan metabolism. It has been shown that miRNAs are involved in cell metastasis through interaction with target mRNAs. In this study, we found 645 miRNAs that could be immunoprecipitated with TDO2 through the RNA-immunoprecipitation experiment. miR-126-5p was selected as the research target, which was also confirmed by dual-luciferase reporter assay. Through qRT-PCR analysis, it was verified that the overexpression of miR-126-5p promoted the expression of TDO2, PI3K/AKT and WNT1. Meanwhile, it was verified that overexpression of miR-126-5p can promote intracellular tryptophan metabolism by HPLC. We also verified the effects of miR-126-5p on cell proliferation, migration, and invasion by cck-8, cell colony formation and trans-well assay in both HCCLM3 cells and HepG2 cells. In vivo experiments were also conducted to verify that miR-126-5p promoted tumor formation and growth via immunohistochemical detection of cell infiltration and proliferation to generate markers Ki-67, BAX, and VEGF. In conclusion, our results suggest that miR-126-5p is a biomarker and a potential new treatment target in the progression of HCC via promoting the expression of TDO2.


2021 ◽  
Vol 5 (2) ◽  
pp. 143-149
Author(s):  
V. M. Sheibak ◽  
◽  
A. Yu. Pauliukavets ◽  

Background. Tryptophan is an essential amino acid found mainly in protein foods and its availability is highly dependent on a diet. A significant part of tryptophan is metabolized in the gastrointestinal tract by the intestinal microbiota, producing a number of biologically active molecules, including aryl hydrocarbon receptor ligands, kynurenines, and serotonin (5-hydroxytryptamine). Objective. To analyze scientific studies confirming the key role of tryptophan microbial catabolites on the function of a macroorganism. Material and methods. The analysis of 47 English-language literature sources containing information on the effects of tryptophan metabolites on the mammalian organism was carried out. Results. It has been established that tryptophan metabolism plays a central role both in a normal macroorganism and in pathological conditions, it being directly or indirectly controlled by the intestinal microbiota. Conclusions. Thus, tryptophan metabolism is an important therapeutic target, underutilized in the treatment of a number of chronic neurological pathologies and immunocompetent conditions. An important factor is the use of nutraceuticals and probiotics by microorganisms that modulate the metabolism of tryptophan in the intestine and stimulate the synthesis of specific metabolites.


Metabolites ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 10
Author(s):  
Yao Lu ◽  
Jasmine Chong ◽  
Shiqian Shen ◽  
Joey-Bahige Chammas ◽  
Lorraine Chalifour ◽  
...  

Crosstalk between the gut microbiome and the host plays an important role in animal development and health. Small compounds are key mediators in this host–gut microbiome dialogue. For instance, tryptophan metabolites, generated by biotransformation of tryptophan through complex host–microbiome co-metabolism can trigger immune, metabolic, and neuronal effects at local and distant sites. However, the origin of tryptophan metabolites and the underlying tryptophan metabolic pathway(s) are not well characterized in the current literature. A large number of the microbial contributors of tryptophan metabolism remain unknown, and there is a growing interest in predicting tryptophan metabolites for a given microbiome. Here, we introduce TrpNet, a comprehensive database and analytics platform dedicated to tryptophan metabolism within the context of host (human and mouse) and gut microbiome interactions. TrpNet contains data on tryptophan metabolism involving 130 reactions, 108 metabolites and 91 enzymes across 1246 human gut bacterial species and 88 mouse gut bacterial species. Users can browse, search, and highlight the tryptophan metabolic pathway, as well as predict tryptophan metabolites on the basis of a given taxonomy profile using a Bayesian logistic regression model. We validated our approach using two gut microbiome metabolomics studies and demonstrated that TrpNet was able to better predict alterations in in indole derivatives compared to other established methods.


Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3469
Author(s):  
Véronique Trézéguet ◽  
Hala Fatrouni ◽  
Aksam J. Merched

Metabolic rewiring in tumor cells is a major hallmark of oncogenesis. Some of the oncometabolites drive suppressive and tolerogenic signals from the immune system, which becomes complicit to the advent and the survival of neoplasia. Tryptophan (TRP) catabolism through the kynurenine (KYN) pathway was reported to play immunosuppressive actions across many types of cancer. Extensive debate of whether the culprit of immunosuppression was the depletion of TRP or rather KYN accumulation in the tumor microenvironment has been ongoing for years. Results from clinical trials assessing the benefit of inhibiting key limiting enzymes of this pathway such as indoleamine 2,3-dioxygenase (IDO1) or tryptophan 2,3-dioxygenase (TDO2) failed to meet the expectations. Bearing in mind the complexity of the tumoral terrain and the existence of different cancers with IDO1/TDO2 expressing and non-expressing tumoral cells, here we present a comprehensive analysis of the TRP global metabolic hub and the driving potential of the process of oncogenesis with the main focus on liver cancers.


Author(s):  
Guan-Ming Lu ◽  
Li-Yuan Jiang ◽  
Dong-Lin Huang ◽  
Yong-Xian Rong ◽  
Yang-Hong Li ◽  
...  

Background: Advanced platelet-rich fibrin extract (APRFE) contains a high concentration of various cytokines that are helpful for improving stem cells repair function. Objective: However, the underlying mechanism of APRFE improving stem cell repairing is not clear. Methods: We produced APRFE by centrifuging fresh peripheral blood samples and isolated and identified human adipose-derived mesenchymal stem cells (ADMSCs). The abundance of cytokines contained in APRFE was detected by the Enzyme-linked immunosorbent assay (ELISA). The ADMSCs treated with or without APRFE were collected for transcriptome sequencing. Results: Based on the sequencing data, the expression profiles were contracted. The differentially expressed genes and lncRNA (DEGs and DElncRNAs) were obtained using for the differential expression analysis. The lncRNA-miRNA-mRNA network was constructed based on the miRNet database. The further enrichment analysis results showed that the biological functions were mainly related to proliferation, differentiation, and cell-cell function. To explore the role of APRFE, the protein-protein interaction network was constructed among the cytokines included in APRFE and DEGs. Furthermore, we constructed the global regulatory network based on the RNAInter and TRRUST database. The pathways in the global regulatory network were considered as the core pathways. We found that the DEGs in the core pathways were associated with stemness scores. Conclusion: In summary, we predicted that APRFE activated three pathways (tryptophan metabolism, mTOR signaling pathway, and adipocytokine signaling) to promote the proliferation and differentiation of ADMSCs. The finding may be helpful for guiding the application of ADMSCs in the clinic.


Author(s):  
Xuehua Xie ◽  
Jiabao Liao ◽  
Yuanliang Ai ◽  
Jinmei Gao ◽  
Jie Zhao ◽  
...  

Pi-Dan-Jian-Qing decoction (PDJQ) can been used in the treatment of type 2 diabetes mellitus (T2DM) in clinic. However, the protective mechanisms of PDJQ on T2DM remain unknown. Recent studies have shown that the changes in gut microbiota could affect the host metabolism and contribute to progression of T2DM. In this study, we first investigated the therapeutic effects of PDJQ on T2DM rats. 16S rRNA sequencing and untargeted metabolomics analyses were used to investigate the mechanisms of action of PDJQ in the treatment of T2DM. Our results showed that PDJQ treatment could improve the hyperglycemia, hyperlipidemia, insulin resistance (IR) and pathological changes of liver, pancreas, kidney, and colon in T2DM rats. PDJQ could also decrease the levels of pro-inflammatory cytokines and inhibit the oxidative stress. 16S rRNA sequencing showed that PDJQ could decrease the Firmicutes/Bacteroidetes (F to B) ratio at the phylum level. At the genus level, PDJQ could increase the relative abundances of Lactobacillus, Blautia, Bacteroides, Desulfovibrio and Akkermansia and decrease the relative abundance of Prevotella. Serum untargeted metabolomics analysis showed that PDJQ could regulate tryptophan metabolism, histidine metabolism, tricarboxylic acid (TCA) cycle, phenylalanine, tyrosine and tryptophan biosynthesis and tyrosine metabolism pathways. Correlation analysis indicated that the modulatory effects of PDJQ on the tryptophan metabolism, histidine metabolism and TCA cycle pathways were related to alterations in the abundance of Lactobacillus, Bacteroides and Akkermansia. In conclusion, our study revealed the various ameliorative effects of PDJQ on T2DM, including improving the liver and kidney functions and alleviating the hyperglycemia, hyperlipidemia, IR, pathological changes, oxidative stress and inflammatory response. The mechanisms of PDJQ on T2DM are likely linked to an improvement in the dysbiosis of gut microbiota and modulation of tryptophan metabolism, histamine metabolism, and the TCA cycle.


NeuroImage ◽  
2021 ◽  
pp. 118842
Author(s):  
Heike Endepols ◽  
Boris D. Zlatopolskiy ◽  
Johannes Zischler ◽  
Nazanin Alavinejad ◽  
Nadine Apetz ◽  
...  

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