Article
Medical Laboratory Technology
Simon Michaelis, Sieglinde Zelzer, Christopher Schneider, Wolfgang J. Schnedl, Andreas Baranyi, Andreas Meinitzer, Markus Herrmann, Dietmar Enko
Summary: The study found that patients with higher activation levels of the kynurenine pathway tended to develop lower anti-SARS-CoV-2 antibody titers.
CLINICA CHIMICA ACTA
(2022)
Review
Clinical Neurology
Magdalena Wiedlocha, Piotr Marcinowicz, Marlena Janoska-Jazdzik, Agata Szulc
Summary: The intestine, together with the gut-associated lymphoid tissue, is the largest immunity organ in the human body, which can be influenced by gut microbiota and lead to the formation of neuroactive metabolites associated with various psychiatric disorders. Current research suggests that probiotics can reduce the toxicity of kynurenine metabolites by affecting proinflammatory cytokines, making gut microbiota a potentially interesting target for future therapies.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2021)
Review
Endocrinology & Metabolism
Carlo Catassi, Giulia Catassi, Loris Naspi
Summary: This review article summarizes recent advances in nonceliac gluten sensitivity (NCGS), a disorder characterized by varied symptoms and frequent irritable bowel syndrome (IBS)-like manifestations. The recent discovery of wheat components other than gluten as disease triggers suggests that nonceliac wheat sensitivity (NCWS) may be a better term. Self-reported NCWS is common, especially in gastroenterology clinic patients, but many diagnoses are not confirmed by standard clinical criteria. A biomarker for NCWS is lacking, although subtle histological features at small intestinal biopsy may aid in diagnosis. Treatment of NCWS is based on the gluten-free diet (GFD), which has proven effective for a significant proportion of NCWS-related IBS patients. Dietary therapies, including the GFD, should be offered by dietitians based on individual patient choice. Studies are underway to test the therapeutic efficacy of supplemental gluten-digesting enzymes in NCWS patients. Recent studies have provided insights into the pathophysiology and clinical features of NCWS, but many questions remain unanswered regarding its epidemiology, biomarkers, and natural history.
CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE
(2023)
Review
Behavioral Sciences
Bing Cao, Yan Chen, Zhongyu Ren, Zihang Pan, Roger S. McIntyre, Dongfang Wang
Summary: The study explored the association between key metabolites of the KYN pathway and schizophrenia, revealing that subjects with prescribed medication had higher KYN levels, higher KYN levels in CSF, lower plasma KYN levels, and higher CSF KYNA levels were associated with SCZ, and KYN levels increased in subjects with SCZ after antipsychotic treatments.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Chemistry, Analytical
Skaidre Jankovskaja, Maxim Morin, Anna Gustafsson, Chris D. Anderson, Boglarka Lehoczki, Johan Engblom, Sebastian Bjorklund, Meinda Rezeli, Gyorgy Marko-Varga, Tautgirdas Ruzgas
Summary: This study assessed various sampling approaches for tryptophan and kynurenine and found that the phenylalanine/tryptophan ratio may be a possible alternative biomarker for non-invasive skin cancer detection.
ANALYTICAL CHEMISTRY
(2022)
Article
Immunology
Clement Adu-Gyamfi, Dana Savulescu, Lillian Mikhathani, Kennedy Otwombe, Nicole Salazar-Austin, Richard Chaisson, Neil Martinson, Jaya George, Melinda Suchard
Summary: The study found that plasma K/T ratio was significantly elevated during pregnancy compared to postpartum samples. Pregnant women who had received isoniazid preventive therapy had lower K/T ratio compared to those who had not, while women with active TB had higher plasma K/T ratio, making it a sensitive blood-based diagnostic test for active TB disease.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Harald Mangge, Markus Herrmann, Andreas Meinitzer, Sabine Pailer, Pero Curcic, Zdenka Sloup, Magdalena Holter, Florian Prueller
Summary: Kynurenine is a promising blood biomarker for predicting mortality risk in severe COVID-19 cases, with KYN levels at the time of SARS-CoV-2 diagnosis serving as an early indicator of poor outcomes. Age, KYN, ferritin, and other markers were found to significantly impact survival time, underscoring the potential of Kynurenine as a prognostic tool in COVID-19 management.
Article
Psychiatry
Handan Noyan, Ece Erdag, Erdem Tuzun, Lhan Yaylim, Ozlem Kucukhuseyin, Mehmet Tolgahan Hakan, Sinan Guloksuz, Bart P. F. Rutten, Meram Can Saka, Cem Atbasoglu, Koksal Alptekin, Jim van Os, Alp Ucok
Summary: The dysregulation of the tryptophan-kynurenine pathway may be an inherited component of schizophrenia, potentially increasing the risk of the disease. Elevated IL-1 beta levels could lead to overconsumption of the pathway, resulting in increased production of neuroregulatory KYNA and possible neurodegeneration.
SCHIZOPHRENIA RESEARCH
(2021)
Article
Medicine, General & Internal
Hani Oweira, Imad Lahdou, Stefan Mehrle, Elias Khajeh, Rajan Nikbakhsh, Omid Ghamarnejad, Peter Terness, Christoph Reissfelder, Mahmoud Sadeghi, Ali Ramouz
Summary: The study revealed that TDO and IDO enzymes have different effects in the conversion of Trp and Kyn in human liver cells and liver cancer cells. Activating the IDO enzyme does not significantly affect Trp degradation and Kyn accumulation, while inhibiting the TDO enzyme significantly reduces Trp degradation.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Immunology
Duygu Eryavuz Onmaz, Abdullah Sivrikaya, Kevser Isik, Sedat Abusoglu, Ilknur Albayrak Gezer, Fatma Humeyra Yerlikaya, Gulsum Abusoglu, Ali Unlu, Dilek Tezcan
Summary: The study found altered kynurenine pathway metabolism in AS patients. Conventional therapy and anti-TNF-alpha therapy are effective in reducing the Kynurenine/Tryptophan ratio and CRP levels.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
La-or Chailurkit, Suwannee Chanprasertyothin, Nisakron Thongmung, Piyamitr Sritara, Boonsong Ongphiphadhanakul
Summary: The present study suggests that the FTO gene may influence the conversion of tryptophan to kynurenine. These findings may contribute to a better understanding of the mechanisms underlying the action of the FTO gene in obesity.
Review
Immunology
Arduino A. Mangoni, Angelo Zinellu
Summary: There is a growing interest in the role of the kynurenine pathway in regulating immune function and inflammation in rheumatic diseases (RD). This study conducted a systematic review and meta-analysis to explore the link between this pathway and RD by examining the levels of tryptophan, kynurenine, and other relevant metabolites in RD patients and healthy controls. The analysis of selected studies revealed significantly lower tryptophan levels and higher kynurenine levels, kynurenine to tryptophan ratios, 3-hydroxykynurenine levels, and quinolinic acid concentrations in RD patients compared to controls. However, the levels of kynurenic acid, 3-hydroxyanthranilic acid, kynurenic acid to kynurenine ratio, and quinolinic acid to kynurenine acid ratio did not show significant differences. Subgroup analysis showed consistent results across different types of RD, except for rheumatoid arthritis. Further research is needed to determine the potential diagnostic and management utility of these biomarkers in RD patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Psychiatry
Junchao Huang, Ping Zhang, Yanfang Zhou, Jinghui Tong, Yimin Cui, Shuping Tan, Zhiren Wang, Fude Yang, Peter Kochunov, Baopeng Tian, Li Tian, L. Elliot Hong, Yunlong Tan
Summary: The study revealed differences in TRP pathway metabolites between patients with TRS and NTRS, with the 5-HT/TRP ratio being associated with clinical symptoms and cognitive performance in TRS patients. This suggests a potential link between an upregulated 5-HT biosynthetic pathway and treatment-resistant schizophrenia, potentially leading to new pharmacological approaches for TRS.
JOURNAL OF PSYCHIATRIC RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Marta Marszalek-Grabska, Katarzyna Walczak, Kinga Gawel, Katarzyna Wicha-Komsta, Sylwia Wnorowska, Artur Wnorowski, Waldemar A. Turski
Summary: KYN, a main metabolite of tryptophan produced mainly in the liver by TDO under physiological conditions, is also synthesized by IDO in diseases. While KYN's role in central nervous system pathologies is well studied, its functions in the periphery are less explored.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Medical Laboratory Technology
Simon Michaelis, Sieglinde Zelzer, Wolfgang J. Schnedl, Andreas Baranyi, Andreas Meinitzer, Dietmar Enko
Summary: Measuring the concentrations of tryptophan and kynurenine upon admission, as well as calculating the KYN/TRP ratio, can predict the survival outcome of patients with SARS-CoV-2.
CLINICA CHIMICA ACTA
(2022)
Article
Neurosciences
Gabriella A. M. Blokland, Jakob Grove, Chia-Yen Chen, Chris Cotsapas, Stuart Tobet, Robert Handa, David St Clair, Todd Lencz, Bryan J. Mowry, Sathish Periyasamy, Murray J. Cairns, Paul A. Tooney, Jing Qin Wu, Brian Kelly, George Kirov, Patrick F. Sullivan, Aiden Corvin, Brien P. Riley, Tonu Esko, Lili Milani, Erik G. Jonsson, Aarno Palotie, Hannelore Ehrenreich, Martin Begemann, Agnes Steixner-Kumar, Pak C. Sham, Nakao Iwata, Daniel R. Weinberger, Pablo Gejman, Alan R. Sanders, Joseph D. Buxbaum, Dan Rujescu, Ina Giegling, Bettina Konte, Annette M. Hartmann, Elvira Bramon, Robin M. Murray, Michele T. Pato, Jimmy Lee, Ingrid Melle, Espen Molden, Roel A. Ophoff, Andrew McQuillin, Nicholas J. Bass, Rolf Adolfsson, Anil K. Malhotra, Nicholas G. Martin, Janice M. Fullerton, Philip B. Mitchell, Peter R. Schofield, Andreas J. Forstner, Franziska Degenhardt, Sabrina Schaupp, Ashley L. Comes, Manolis Kogevinas, Jose Guzman-Parra, Andreas Reif, Fabian Streit, Lea Sirignano, Sven Cichon, Maria Grigoroiu-Serbanescu, Joanna Hauser, Jolanta Lissowska, Fermin Mayoral, Bertram Muller-Myhsok, Thomas G. Schulze, Markus M. Nothen, Marcella Rietschel, John Kelsoe, Marion Leboyer, Stephane Jamain, Bruno Etain, Frank Bellivier, John B. Vincent, Martin Alda, Claire O'Donovan, Pablo Cervantes, Joanna M. Biernacka, Mark Frye, Susan L. McElroy, Laura J. Scott, Eli A. Stahl, Mikael Landen, Marian L. Hamshere, Olav B. Smeland, Srdjan Djurovic, Arne E. Vaaler, Ole A. Andreassen, Bernhard T. Baune, Tracy Air, Martin Preisig, Rudolf Uher, Douglas F. Levinson, Myrna M. Weissman, James B. Potash, Jianxin Shi, James A. Knowles, Roy H. Perlis, Susanne Lucae, Dorret Boomsma, Brenda W. J. H. Penninx, Jouke-Jan Hottenga, Eco J. C. de Geus, Gonneke Willemsen, Yuri Milaneschi, Henning Tiemeier, Hans J. Grabe, Alexander Teumer, Sandra Van der Auwera, Uwe Volker, Steven P. Hamilton, Patrik K. E. Magnusson, Alexander Viktorin, Divya Mehta, Niamh Mullins, Mark J. Adams, Gerome Breen, Andrew M. McIntosh, Cathryn M. Lewis, David M. Hougaard, Merete Nordentoft, Ole Mors, Preben B. Mortensen, Thomas Werge, Thomas D. Als, Anders D. Borglum, Tracey L. Petryshen, Jordan W. Smoller, Jill M. Goldstein
Summary: The study found significant sex-dependent genetic risk in schizophrenia, major depressive disorder, and bipolar disorder, with implications for genes related to neuronal development, immune functions, and vascular functions across and within these disorders. This suggests substantial genetic overlap between sexes in mood and psychotic disorders, with sex-specific effects enriched for genes involved in various physiological functions.
BIOLOGICAL PSYCHIATRY
(2022)
Review
Chemistry, Medicinal
Frederike T. Fellendorf, Nina Bonkat, Nina Dalkner, Elena M. D. Schoenthaler, Mirko Manchia, Dietmar Fuchs, Eva Z. Reininghaus
Summary: This review highlights the inconsistent findings on KYN/TRP ratio in severe mental disorders. Although there are indications of inflammation associated with elevated IDO activity, no conclusive statements can be made. Considering factors such as inflammatory processes, metabolic activities, and psychological/neuropsychiatric symptoms are crucial for a deeper understanding of the underlying mechanisms.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Mutaz Amin, Jurg Ott, Rongling Wu, Teodor T. Postolache, Claudia Gragnoli
Summary: Melanocortin receptor genes are associated with the risk of major depressive disorder (MDD) and type 2 diabetes (T2D). This study found that MC2R and MC5R genes are associated with MDD, while MC1R, MC2R, MC3R, and MC4R genes are associated with T2D. These findings provide important insights into the role of melanocortin receptor genes in the comorbidity of MDD and T2D.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Mutaz Amin, Jurg Ott, Derek Gordon, Rongling Wu, Teodor T. Postolache, Michael Vergare, Claudia Gragnoli
Summary: Variants of the CRHR2 gene are associated with the risk of depression and type 2 diabetes. This study identified novel risk variants related to depression and type 2 diabetes in 212 Italian families. The findings suggest that CRHR2 plays a stronger role in the risk of depression than in the risk of type 2 diabetes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Mutaz Amin, Shumail Syed, Rongling Wu, Teodor Tudorel Postolache, Claudia Gragnoli
Summary: Impairment in the HPA axis and cortisol pathway may contribute to the development of major depressive disorders and type 2 diabetes. Variants in the NR3C1 gene are associated with the risk of T2D-MDD comorbidity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Cornelia A. Karg, Lucia Parrakova, Dietmar Fuchs, Harald Schennach, Bernhard Kraeutler, Simone Moser, Johanna M. Gostner
Summary: Phyllobilins, derived from the degradation of chlorophyll, are natural products with antioxidant and immunomodulatory properties. However, their mechanisms of action and in vivo effects require further investigation.
Article
Microbiology
Laura P. Kincer, Sarah Beth Joseph, Maria M. Gilleece, Blake M. Hauser, Sabrina Sizemore, Shuntai Zhou, Clara Di Germanio, Henrik Zetterberg, Dietmar Fuchs, Steven G. Deeks, Serena Spudich, Magnus Gisslen, Richard W. Price, Ronald Swanstrom
Summary: HIV-1 can persist in a latent reservoir in individuals receiving antiretroviral therapy, and rebound virus can be detected in the cerebrospinal fluid during treatment interruption. In this study, we found that high viral loads and clonally amplified viral lineages in the cerebrospinal fluid were correlated with the influx of white blood cells. Additionally, we did not observe rebound macrophage-tropic virus in the cerebrospinal fluid, indicating that the CNS may not be a source of this virus. We propose a model in which R5 T cell-tropic virus is released from infected T cells in the CNS during treatment interruption.
NATURE MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Andrew J. Hoisington, Christopher E. Stamper, Katherine L. Bates, Maggie A. Stanislawski, Michael C. Flux, Teodor T. Postolache, Christopher A. Lowry, Lisa A. Brenner
Summary: Compared to other skin sites, the bacterial microbiome on the human hand shows greater variability over time. This study collected skin microbiome samples from 22 participants' dominant hands, frequently touched objects, and infrequently touched objects in office environments, as well as longitudinal samples from a subset of 11 participants' home environments. The results revealed stable microbiomes in both hand and built environments within office and home settings, but differences in microbial communities were found across different built environments. Occupants' frequency of touching objects correlated with a higher presence of human microbes on those objects, but the percentage of shared microbes varied among participants. Furthermore, horizontal surfaces in the built environment had higher microbial diversity compared to objects and the occupants' hands.
SCIENTIFIC REPORTS
(2023)
Article
Immunology
Arvid Eden, Frida Rydberg, Aylin Yilmaz, Lars Hagberg, Johanna Gostner, Staffan Nilsson, Dietmar Fuchs, Magnus Gisslen
Summary: For people with HIV initiating ART during chronic infection, the occurrence of residual CNS immune activation is not correlated with pretreatment immune status, even when treatment is initiated at high CD4(+) T-cell counts, suggesting that the CNS reservoir is not differentially affected by the timing of ART initiation during chronic infection.
OPEN FORUM INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Katharina Obermoser, Natascha Brigo, Andrea Schroll, Pablo Monfort-Lanzas, Johanna M. Gostner, Sabine Engl, Simon Geisler, Miriam Knoll, Harald Schennach, Guenter Weiss, Dietmar Fuchs, Rosa Bellmann-Weiler, Katharina Kurz
Summary: This pilot study investigated the effects of a multi-strain probiotic preparation on fatigue, depression, and quality of life in patients with post-infectious fatigue. The results showed that both the probiotic and placebo groups experienced improvements, but the probiotic group had greater improvements. After 6 months, the probiotic group had significantly lower fatigue and depression scores, as well as improved quality of life.
Editorial Material
Medicine, General & Internal
Andrew J. Hoisington, Christopher Lowry, Lindsay T. Mcdonald, Silpa D. Krefft, Cecile S. Rose, Elizabeth J. Kovacs, Lisa A. Brenner
Summary: The First Annual PACT Act Research Symposium for Veteran Health in Colorado focused on the impacts of military exposures on respiratory and mental health. The symposium highlighted the dearth of research on psychological health among veterans and called for a life-course approach in addressing physical and psychological exposures.
Article
Immunology
Andrew J. Hoisington, Christopher E. Stamper, Kelly A. Stearns-Yoder, Fatemeh Haghighi, Christopher A. Lowry, Lisa A. Brenner
Summary: While many studies have focused on intestinal permeability in individuals with gastrointestinal disorders, there is a rising trend to analyze it in individuals with mental health conditions, including posttraumatic stress disorder (PTSD). This study investigated blood-based biomarkers of intestinal permeability and their association with PTSD symptoms. However, the results showed no significant correlation between these biomarkers and the severity of PTSD symptoms.
BRAIN BEHAVIOR & IMMUNITY-HEALTH
(2023)
Article
Medicine, Research & Experimental
Lisa A. Brenner, Kelly A. Stearns-Yoder, Christopher E. Stamper, Andrew J. Hoisington, Diana P. Brostow, Claire A. Hoffmire, Jeri E. Forster, Meghan L. Donovan, Arthur T. Ryan, Teodor T. Postolache, Christopher A. Lowry
Summary: This article describes the rationale, design, and methods of a randomized placebo-controlled trial of Lactobacillus rhoosus GG for posttraumatic stress disorder (PTSD) in United States military Veterans. The trial aims to reduce inflammation and alleviate symptoms of PTSD through the use of immunoregulatory/antiinflammatory probiotics, providing evidence for this innovative intervention strategy.
CONTEMPORARY CLINICAL TRIALS COMMUNICATIONS
(2022)
Review
Microbiology
Jake M. Robinson, Nicole Redvers, Araceli Camargo, Christina A. Bosch, Martin F. Breed, Lisa A. Brenner, Megan A. Carney, Ashvini Chauhan, Mauna Dasari, Leslie G. Dietz, Michael Friedman, Laura Grieneisen, Andrew J. Hoisington, Patrick F. Horve, Ally Hunter, Sierra Jech, Anna Jorgensen, Christopher A. Lowry, Ioana Man, Gwynne Mhuireach, Edauri Navarro-Perez, Euan G. Ritchie, Justin D. Stewart, Harry Watkins, Philip Weinstein, Suzanne L. Ishaq
Summary: This study aims to summarize and stimulate research on microbial exposure and social equity, providing focus for funders and policymakers.