ReviewInternational journal of molecular sciences2021
Tryptophan Metabolites and Aryl Hydrocarbon Receptor in Severe Acute Respiratory Syndrome, Coronavirus-2 (SARS-CoV-2) Pathophysiology.
Review in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Gut microbiota metabolites in the immunoregulation of enteritis: research progress.Frontiers in immunology · 2025Pooled it
- Nicotinamide modulates gut microbial metabolic potential and accelerates recovery in mild-to-moderate COVID-19.Nature metabolism · 2025Trial
- Metabolic control of macrophages in coronavirus disease 2019.Virulence · 2026Review
- Integrating host-microbiota metabolic networks: how aromatic amino acids shape immune homeostasis and affect disease progression.Cellular & molecular immunology · 2026Review
- Inducible CD147 up-regulation boosts extended SARS-CoV-2 infection triggering severe COVID-19 independent of ACE2.Signal transduction and targeted therapy · 2026Article
- Clocking immunity: circadian modulation of NK cells and emerging timing perspectives.Frontiers in immunology · 2026Review
- Glioblastoma pathophysiology: roles of aging driven changes in STAT3 interactions with NF-κB dimer components in the modulation of the mitochondrial melatonergic pathway and night-time inflammation resolution.Exploration of targeted anti-tumor therapy · 2026Review
- Exploring the Interplay Between Gut Microbiota and the Melatonergic Pathway in Hormone Receptor-Positive Breast Cancer.International journal of molecular sciences · 2025Article
- Indole metabolism and its role in diabetic macrovascular and microvascular complications.American heart journal plus : cardiology research and practice · 2025Review
- Could a Mediterranean Diet Modulate Alzheimer's Disease Progression? The Role of Gut Microbiota and Metabolite Signatures in Neurodegeneration.Foods (Basel, Switzerland) · 2025Review
- The role of aryl hydrocarbon receptor signalling in COVID-19 pathology and its therapeutic potential.Frontiers in molecular medicine · 2025Review
- Prenatal Poly I:C exposure affects tryptophan-kynurenine metabolism associated with intestinal microbiome in female juvenile rats.Frontiers in immunology · 2025Article
- Aryl Hydrocarbon Receptor Activation in Pulmonary Alveolar Epithelial Cells Limits Inflammation and Preserves Lung Epithelial Cell Integrity.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Aryl hydrocarbon receptor activation alters immune cell populations in the lung and bone marrow during coronavirus infection.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Metabolomic landscape of macrophage discloses an anabolic signature of dengue virus infection and antibody-dependent enhancement of viral infection.PLoS neglected tropical diseases · 2024Article
- Metabolic alterations in urine among the patients with severe fever with thrombocytopenia syndrome.Virology journal · 2024Article
- Role of aryl hydrocarbon receptors in infection and inflammation.Frontiers in immunology · 2024Review
- Signal Pathways and microRNAs in Osteosarcoma Growth and the Dual Role of Mesenchymal Stem Cells in Oncogenesis.International journal of molecular sciences · 2023Review
- Review
- An untargeted metabolomic approach to investigate antiviral defence mechanisms in memory leukocytes secreting anti-SARS-CoV-2 IgG in vitro.Scientific reports · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The metabolism of tryptophan is intimately associated with the differential regulation of diverse physiological processes, including in the regulation of responses to severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) infection that underpins the COVID-19 pandemic. Two important products of tryptophan metabolism, viz kynurenine and interleukin (IL)4-inducible1 (IL41)-driven indole 3 pyruvate (I3P), activate the aryl hydrocarbon receptor (AhR), thereby altering the nature of immune responses to SARS-CoV-2 infection. AhR activation dysregulates the initial pro-inflammatory cytokines production driven by neutrophils, macrophages, and mast cells, whilst AhR activation suppresses the endogenous antiviral responses of natural killer cells and CD8+ T cells. Such immune responses become further dysregulated by the increased and prolonged pro-inflammatory cytokine suppression of pineal melatonin production coupled to increased gut dysbiosis and gut permeability. The suppression of pineal melatonin and gut microbiome-derived butyrate, coupled to an increase in circulating lipopolysaccharide (LPS) further dysregulates the immune response. The AhR mediates its effects via alterations in the regulation of mitochondrial function in immune cells. The increased risk of severe/fatal SARS-CoV-2 infection by high risk conditions, such as elderly age, obesity, and diabetes are mediated by these conditions having expression levels of melatonin, AhR, butyrate, and LPS that are closer to those driven by SARS-CoV-2 infection. This has a number of future research and treatment implications, including the utilization of melatonin and nutraceuticals that inhibit the AhR, including the polyphenols, epigallocatechin gallate (EGCG), and resveratrol.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.