Gut microbiota, kynurenine pathway and mental disorders - Review.
02 Mar 2021-Progress in Neuro-psychopharmacology & Biological Psychiatry (Elsevier)-Vol. 106, pp 110145
TL;DR: In this article, the authors highlight the current knowledge on the interaction of gut microbiota and the central nervous system with the kynurenine pathway taken into special account, and present up-to-date study results on specific psychiatric disorders such as schizophrenia, bipolar disorder, Alzheimer's disease, autism spectrum disorders, depression and alcoholism.
Abstract: The intestine and the gut-associated limphoid tissue constitute the largest immunity organ of the human body. Among several possible tryptophan metabolism routes, the kynurenine pathway can be influenced by the gut microbiota. Disturbances of gut biodiversity may cause increased gut permeability and cause systemic inflammation, also related to central nervous system. Proinflammatory cytokines induce kynurenine pathway enzymes resulting in formation of neuroactive metabolites, which are being associated with several psychiatric disorders. The kynurenine pathway may also be influenced by certain bacteria species directly. The aim of this review is to highlight the current knowledge on the interaction of gut microbiota and the central nervous system with the kynurenine pathway taken into special account. Up to date study results on specific psychiatric disorders such as schizophrenia, bipolar disorder, Alzheimer's disease, autism spectrum disorders, depression and alcoholism are presented. Available evidence suggests that toxicity of kynurenine metabolites may be reduced by adjunction of probiotics which can affect proinflammatory cytokines. Due to their potential for modulation of the kynurenine pathway, gut microbiota pose an interesting target for future therapies.
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TL;DR: This review aims to present a comprehensive overview of the potential involvement of the human gut microbiome in the pathogenesis of neurological disorders, with a particular emphasis on the potential of microbe-based therapies and/or diagnostic microbial biomarkers.
Abstract: The human body is full of an extensive number of commensal microbes, consisting of bacteria, viruses, and fungi, collectively termed the human microbiome. The initial acquisition of microbiota occurs from both the external and maternal environments, and the vast majority of them colonize the gastrointestinal tract (GIT). SUMMARY The human body is full of an extensive number of commensal microbes, consisting of bacteria, viruses, and fungi, collectively termed the human microbiome. The initial acquisition of microbiota occurs from both the external and maternal environments, and the vast majority of them colonize the gastrointestinal tract (GIT). These microbial communities play a central role in the maturation and development of the immune system, the central nervous system, and the GIT system and are also responsible for essential metabolic pathways. Various factors, including host genetic predisposition, environmental factors, lifestyle, diet, antibiotic or nonantibiotic drug use, etc., affect the composition of the gut microbiota. Recent publications have highlighted that an imbalance in the gut microflora, known as dysbiosis, is associated with the onset and progression of neurological disorders. Moreover, characterization of the microbiome-host cross talk pathways provides insight into novel therapeutic strategies. Novel preclinical and clinical research on interventions related to the gut microbiome for treating neurological conditions, including autism spectrum disorders, Parkinson’s disease, schizophrenia, multiple sclerosis, Alzheimer’s disease, epilepsy, and stroke, hold significant promise. This review aims to present a comprehensive overview of the potential involvement of the human gut microbiome in the pathogenesis of neurological disorders, with a particular emphasis on the potential of microbe-based therapies and/or diagnostic microbial biomarkers. This review also discusses the potential health benefits of the administration of probiotics, prebiotics, postbiotics, and synbiotics and fecal microbiota transplantation in neurological disorders.
55 citations
TL;DR: In this paper, the relationship between depression and the tryptophan-kynurenine metabolic pathway is overviewed in the light of recent publications, among which kynerunic acid (KYNA) and quinolinic acid (QUIN) are molecules of great interest in recent studies on the mechanisms of inflammationinduced depression.
Abstract: Inflammatory bowel disease (IBD), which mainly includes ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic bowel diseases that are characterized by abdominal pain, diarrhea, and bloody stools. IBD is strongly associated with depression, and its patients have a higher incidence of depression than the general population. Depression also adversely affects the quality of life and disease prognosis of patients with IBD. The tryptophan-kynurenine metabolic pathway degrades more than 90% of tryptophan (TRP) throughout the body, with indoleamine 2,3-dioxygenase (IDO), the key metabolic enzyme, being activated in the inflammatory environment. A series of metabolites of the pathway are neurologically active, among which kynerunic acid (KYNA) and quinolinic acid (QUIN) are molecules of great interest in recent studies on the mechanisms of inflammation-induced depression. In this review, the relationship between depression in IBD and the tryptophan-kynurenine metabolic pathway is overviewed in the light of recent publications.
51 citations
TL;DR: In this paper, the effects of α-lactalbumin (ALAC), a prebiotic in the dose range of 125-500mg/kg, and sodium butyrate (NaB) alone and in combination were investigated for idiopathic autism and anxiety/depression.
24 citations
TL;DR: In this paper, a bibliometric analysis aimed to provide a first glimpse into the dysregulated kynurenine pathway (KP), an immune-inflammatory pathway, in the pathophysiology of mood disorders, including depression and bipolar disorder characterized by a low-grade chronic pro-inflammatory state.
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.
19 citations
TL;DR: In this paper, a secondary analysis of previous data concerning microbiome and metabolomics profiles of 17 anorexia nervosa (ANR) women, six binge-purging AN (ANBP) women and 20 healthy controls (HC).
Abstract: Alterations in the gut microbiome and fecal metabolites have been detected in anorexia nervosa (AN), but differences in those profiles between restricting AN (ANR) and binge-purging AN (ANBP) type have not been explored. We made a secondary analysis of our previous data concerning microbiome and metabolomics profiles of 17 ANR women, six ANBP women and 20 healthy controls (HC). Twelve fecal metabolites differentiating ANR patients, ANBP patients and HC were identified. Both patient groups showed decreased intra-individual bacterial richness with respect to healthy controls (HC). Compared to ANR subjects, ANBP patients had a significant increase in relative abundances of Bifidobacterium, Bifidobacteriaceae, Bifidobacteriales, and Eubacteriacae and a significant decrease in relative abundances of Odoribacter, Haemophilus, Pasteurellaceae, and Pasteurellales. The heatmaps of the relationships of selected fecal metabolites with microbial families showed different structures among the three groups, with the heatmap of ANBP patients being drastically different from that of HC, while that of ANR patients resulted more similar to HC. These findings, although preliminary because of the relatively small sample size, confirm the occurrence of different gut dysbiosis in ANR and ANBP and demonstrate different connections between gut microorganisms and fecal metabolites in the two AN types.
19 citations
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