Comprehensive Bibliometric Analysis of the Kynurenine Pathway in Mood Disorders: Focus on Gut Microbiota Research

Abstract

Background: Emerging evidence implicates the dysregulated kynurenine pathway (KP), an immune-inflammatory pathway, in the pathophysiology of mood disorders (MD), including depression and bipolar disorder characterized by a low-grade chronic pro-inflammatory state. The metabolites of the KP, an important part of the microbiota-gut-brain axis, serve as immune system modulators linking the gut microbiota (GM) with the host central nervous system.Aim: This bibliometric analysis aimed to provide a first glimpse into the KP in MD, with a focus on GM research in this field, to guide future research and promote the development of this field.Methods: Publications relating to the KP in MD between the years 2000 and 2020 were retrieved from the Scopus and Web of Science Core Collection (WoSCC), and analyzed in CiteSpace (5.7 R5W), biblioshiny (using R-Studio), and VOSviewer (1.6.16).Results: In total, 1,064 and 948 documents were extracted from the Scopus and WoSCC databases, respectively. The publications have shown rapid growth since 2006, partly owing to the largest research hotspot appearing since then, “quinolinic acid.” All the top five most relevant journals were in the neuropsychiatry field, such as Brain Behavior and Immunity. The United States and Innsbruck Medical University were the most influential country and institute, respectively. Journal co-citation analysis showed a strong tendency toward co-citation of research in the psychiatry field. Reference co-citation analysis revealed that the top four most important research focuses were “kynurenine pathway,” “psychoneuroimmunology,” “indoleamine 2,3-dioxygenase,” and “proinflammatory cytokines,” and the most recent focus was “gut-brain axis,” thus indicating the role of the KP in bridging the GM and the host immune system, and together reflecting the field’s research foundations. Overlap analysis between the thematic map of keywords and the keyword burst analysis revealed that the topics “Alzheimer’s disease,” “prefrontal cortex,” and “acid,” were research frontiers.Conclusion: This comprehensive bibliometric study provides an updated perspective on research associated with the KP in MD, with a focus on the current status of GM research in this field. This perspective may benefit researchers in choosing suitable journals and collaborators, and aid in the further understanding of the field’s hotspots and frontiers, thus facilitating future research.

Combining Metabolomics and Interpretable Machine Learning to Reveal Plasma Metabolic Profiling and Biological Correlates of Alcohol-Dependent Inpatients: What About Tryptophan Metabolism Regulation?

“…-Puerto et al, 2021). Moreover, given that the imbalance of neuroprotective and neurotoxic kynurenine pathway metabolites is associated with the pathogenesis of neuropsychiatric disorders (Myint et al, 2007;Muneer, 2020;Zhu et al, 2021a), the disturbances of tryptophan metabolism along the kynurenine pathway may contribute to the cooccurrence of alcohol exposure and mental disorders in the context of addiction (Neupane et al, 2015;Jiang et al, 2020;Vidal et al, 2020).…”

“…The kynurenine pathway accounts for above 95% of the host tryptophan metabolism, mediated by the indolamine 2,3-dioxygenase expressed in most tissues and the tryptophan 2,3-dioxygenase that is found mainly in the liver ( Yamazaki et al, 1985 ). This leads to producing an array of downstream metabolites called “kynurenines,” including kynurenic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and quinolinic acid ( Zhu et al, 2021a ). Studies have been conducted on the links between alcohol exposure and tryptophan metabolism, though they mainly focused on the tryptophan/serotonin pathway ( LeMarquand et al, 1994 ; Morales-Puerto et al, 2021 ).…”

“…For example, kynurenic acid could counteract the drug abuse-associated addictive effects by regulating glutamatergic transmission via acting at several potential receptors on the brain, such as the N-Methyl- d -Aspartate (NMDA) receptor ( Morales-Puerto et al, 2021 ). Moreover, given that the imbalance of neuroprotective and neurotoxic kynurenine pathway metabolites is associated with the pathogenesis of neuropsychiatric disorders ( Myint et al, 2007 ; Muneer, 2020 ; Zhu et al, 2021a ), the disturbances of tryptophan metabolism along the kynurenine pathway may contribute to the co-occurrence of alcohol exposure and mental disorders in the context of addiction ( Neupane et al, 2015 ; Jiang et al, 2020 ; Vidal et al, 2020 ).…”

Association between intestinal microbiome and inflammatory bowel disease: Insights from bibliometric analysis

“…The role of changes in intestinal microbes in the pathogenesis of IBD has attracted increasing attention, making intestinal microbes a research hotspot in the field of IBD in the past two decades. Currently, bibliometric analysis is increasingly being used to examine the status and trends of specific fields [28] , [29] . However, to date, no bibliometric analysis has been conducted in the field of IBD, particularly on the research of intestinal microbes in this field.…”

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“…The kynurenine pathway accounts for above 95% of the host tryptophan metabolism, mediated by the indolamine 2,3dioxygenase expressed in most tissues and the tryptophan 2,3-dioxygenase that is found mainly in the liver (Yamazaki et al, 1985). This leads to producing an array of downstream metabolites called "kynurenines," including kynurenic acid, 3hydroxykynurenine, 3-hydroxyanthranilic acid, and quinolinic acid (Zhu et al, 2021a). Studies have been conducted on the links between alcohol exposure and tryptophan metabolism, though they mainly focused on the tryptophan/serotonin pathway (LeMarquand et al, 1994;Morales-Puerto et al, 2021).…”