Immune-Kynurenine Pathways and the Gut Microbiota-Brain Axis in Anxiety Disorders

Evrensel, Alper; Ünsalver, Barış Önen; Ceylan, Mehmet Emin

doi:10.1007/978-981-32-9705-0_10

Cited by 27 publications

(16 citation statements)

References 110 publications

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“…Mice with fecal microbial transplant from depressed patients demonstrate worse anxiety in association with higher circulating kynurenine and kynurenine/TPH ratios [ 155 , 156 ]. Interestingly, chronic stress is known to increase circulating TPH and cortisol, resulting in shunting of serotonin metabolism toward kynurenine and its metabolites due to enhanced glucocorticoid-induced TDO expression [ 157 ].…”

Section: Tryptophan Metabolites In Neurodevelopment Neurologic Anmentioning

confidence: 99%

“…Findings from induction of stress in mice showed that exogenous butyrate regulated stress-induced depressive behavior, decreased hippocampal serotonin and increased hippocampal brain-derived neurotrophic factor (BDNF) [ 158 , 159 ]. Mice whose gut microbiota was depleted with antibiotic cocktails demonstrated anxiety-like behaviors and elevated circulating kynurenine [ 156 ]. In obese rats fed a high-fat diet, anthocyanins protected against neuroinflammation and also exhibited reduced circulating TPH and increases in KA [ 160 ].…”

Section: Tryptophan Metabolites In Neurodevelopment Neurologic Anmentioning

confidence: 99%

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Tryptophan Metabolism and Gut-Brain Homeostasis

Roth

Zadeh

Vekariya

et al. 2021

IJMS

168

142

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Tryptophan is an essential amino acid critical for protein synthesis in humans that has emerged as a key player in the microbiota-gut-brain axis. It is the only precursor for the neurotransmitter serotonin, which is vital for the processing of emotional regulation, hunger, sleep, and pain, as well as colonic motility and secretory activity in the gut. Tryptophan catabolites from the kynurenine degradation pathway also modulate neural activity and are active in the systemic inflammatory cascade. Additionally, tryptophan and its metabolites support the development of the central and enteric nervous systems. Accordingly, dysregulation of tryptophan metabolites plays a central role in the pathogenesis of many neurologic and psychiatric disorders. Gut microbes influence tryptophan metabolism directly and indirectly, with corresponding changes in behavior and cognition. The gut microbiome has thus garnered much attention as a therapeutic target for both neurologic and psychiatric disorders where tryptophan and its metabolites play a prominent role. In this review, we will touch upon some of these features and their involvement in health and disease.

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Section: Tryptophan Metabolites In Neurodevelopment Neurologic Anmentioning

confidence: 99%

Section: Tryptophan Metabolites In Neurodevelopment Neurologic Anmentioning

confidence: 99%

Tryptophan Metabolism and Gut-Brain Homeostasis

Roth

Zadeh

Vekariya

et al. 2021

IJMS

168

142

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“…The absolute and relative concentrations of kynurenines vary among different cell types due to different enzymatic repertoires ( 19 ). These Trp catabolites are activated in times of stress and inflammation ( 21 ). Three important rate-limiting enzymes indoleamine 2, 3-dioxygenase 1 and 2 (IDO1 and IDO2), and TDO utilize Trp as a substrate and generate N-formylkynurenine during the initial steps on Trp catabolism.…”

Section: Tryptophan/kynurenine Metabolismmentioning

confidence: 99%

“…In hepatocytes TDO expression is stimulated by glucocorticoids. In contrast, the IDO1 present outside the liver is stimulated by proinflammatory cytokines ( 21 ). In the majority of cell types, IDO expression is induced by proinflammatory modulators, such as lipopolysaccharide (LPS), tumor necrosis factor-α (TNFα), interleukin 1 (IL-1), and IL-2 ( 23 , 24 ).…”

Section: Tryptophan/kynurenine Metabolismmentioning

confidence: 99%

Tryptophan Catabolism and Inflammation: A Novel Therapeutic Target For Aortic Diseases

et al. 2021

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Aortic diseases are the primary public health concern. As asymptomatic diseases, abdominal aortic aneurysm (AAA) and atherosclerosis are associated with high morbidity and mortality. The inflammatory process constitutes an essential part of a pathogenic cascade of aortic diseases, including atherosclerosis and aortic aneurysms. Inflammation on various vascular beds, including endothelium, smooth muscle cell proliferation and migration, and inflammatory cell infiltration (monocytes, macrophages, neutrophils, etc.), play critical roles in the initiation and progression of aortic diseases. The tryptophan (Trp) metabolism or kynurenine pathway (KP) is the primary way of degrading Trp in most mammalian cells, disturbed by cytokines under various stress. KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), etc. Depends on the cell types, these metabolites can elicit both hyper- and anti-inflammatory effects. Accumulating evidence obtained from various animal disease models indicates that KP contributes to the inflammatory process during the development of vascular disease, notably atherosclerosis and aneurysm development. This review outlines current insights into how perturbed Trp metabolism instigates aortic inflammation and aortic disease phenotypes. We also briefly highlight how targeting Trp metabolic pathways should be considered for treating aortic diseases.

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“…Classical conceptualizations of stress and depression have attributed such changes to the associated decrease in brain serotonin as well as to the neuroregulatory effects of kynurenine pathway products, such kynurenic acid and quinolinic acid [ 38 ]. However, there is a growing appreciation that even classical psychiatric disorders—such as depression [ 39 , 40 ], anxiety [ 41 ], and schizophrenia [ 42 ]—are powerfully determined by alterations in the kynurenine pathway and the AhR regulation of the immune system. The role of neuronal activity in mediating stress/depression has now shifted to viewing neuronal activity more as a form of ‘immune-to-immune’ communication [ 43 ].…”

Section: Sars-cov-2 Entry and Pathophysiologymentioning

confidence: 99%

Aryl Hydrocarbon Receptor Role in Co-Ordinating SARS-CoV-2 Entry and Symptomatology: Linking Cytotoxicity Changes in COVID-19 and Cancers; Modulation by Racial Discrimination Stress

Anderson¹,

Carbone

Mazzoccoli

2020

Biology

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There is an under-recognized role of the aryl hydrocarbon receptor (AhR) in co-ordinating the entry and pathophysiology of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) that underpins the COVID-19 pandemic. The rise in pro-inflammatory cytokines during the ‘cytokine storm’ induce indoleamine 2,3-dioxygenase (IDO), leading to an increase in kynurenine that activates the AhR, thereby heightening the initial pro-inflammatory cytokine phase and suppressing the endogenous anti-viral response. Such AhR-driven changes underpin the heightened severity and fatality associated with pre-existent high-risk medical conditions, such as type II diabetes, as well as to how racial discrimination stress contributes to the raised severity/fatality in people from the Black Asian and Minority Ethnic (BAME) communities. The AhR is pivotal in modulating mitochondrial metabolism and co-ordinating specialized, pro-resolving mediators (SPMs), the melatonergic pathways, acetyl-coenzyme A, and the cyclooxygenase (COX) 2-prostaglandin (PG) E2 pathway that underpin ‘exhaustion’ in the endogenous anti-viral cells, paralleling similar metabolic suppression in cytolytic immune cells that is evident across all cancers. The pro-inflammatory cytokine induced gut permeability/dysbiosis and suppression of pineal melatonin are aspects of the wider pathophysiological underpinnings regulated by the AhR. This has a number of prophylactic and treatment implications for SARS-CoV-2 infection and cancers and future research directions that better investigate the biological underpinnings of social processes and how these may drive health disparities.

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Immune-Kynurenine Pathways and the Gut Microbiota-Brain Axis in Anxiety Disorders

Cited by 27 publications

References 110 publications

Tryptophan Metabolism and Gut-Brain Homeostasis

Tryptophan Metabolism and Gut-Brain Homeostasis

Tryptophan Catabolism and Inflammation: A Novel Therapeutic Target For Aortic Diseases

Aryl Hydrocarbon Receptor Role in Co-Ordinating SARS-CoV-2 Entry and Symptomatology: Linking Cytotoxicity Changes in COVID-19 and Cancers; Modulation by Racial Discrimination Stress

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