AHR {90000236}

Shared Reference Notes

• [1.1] [#Alzheimer’s disease, #Parkinson’s Disease] 
  - #Tryptophan metabolites can cross the blood-brain barrier > activate AHR to regulate astrocytes and reduce central nervous system inflammation in AD and PD
• [#Cancer] - AHR and its ligand activators have shown procancer activity, and ligand antagonists of AHR have the potential to become anticancer drugs
• [1.2] 
  - AHR is expressed by keratinocytes, epidermal Langerhans cells, dermal and epidermal innate and adaptive immune cells. - The activation of AHR is mostly anti-inflammatory through the regulation of cytokine production and other immune-related transcription factors, such as NF-κB. - In the skin epidermis, dead keratinocytes and broken keratin are used as substrates in the #Tryptophan metabolism of skin microbiota which leads to AHR agonists production
• [1.3] 
  - 3,4,5-trihydroxybenzoic acid (#Gallic acid), a gut metabolite, but also a parent compound present in some fruits (i.e., berries), is one of the most studied metabolites as an AhR modulator > reduce inflammatory responses and cancer spread.
• - 3,8-Dihydroxy-urolithin (#Urolithin A), a metabolite of #Ellagic acid which is found in high levels in pomegranate, acts on the AHR and nuclear factor erythroid 2–related factor 2 (NRF2) signalling pathways to upregulate the expression of TJs proteins and ameliorate #Colitis - #Urolithin A is an agonist of AhR able to reduce the expression of inflammatory genes.
• [1.4] [#Agavins, #Polyphenols] [#Cranberry] 
  - The combination of CP+AG significantly increased the expression of aryl hydrocarbon receptors (Ahr).
• [1.5] [#Indole-3-acetic acid, #Pyruvic acids] 
  - AHR, especially in barrier tissues of the respiratory and gastrointestinal, can also be activated by dietary and microbial indole-derived metabolites such as pyruvic acid (IPyA), indole acetic acid (IAA), #Indoxyl-3-sulfate, #Indole-3-carbinole (I3C), and 3,3′-di-indolylmethane (DIM).
• [#Indole, #Tryptophan] - Indoles, generated by commensal microbes, also serve as AHR agonists and therefore are likely to influence immune homeostasis as well as anticancer immunity.
• - #kynurenine is an effective agonist and the #Tryptophan photo-oxidation product 6-formylindolo[3,2-b]carbazole (FICZ) is one of the most potent endogenous AHR agonists
• [1.6] [#kynurenine] 
  - T-cell differentiation and activation is reduced when AhR is activated on the T cells by KYN
• [1.7] 
  - Endothelial AHR-deficiency in adult mice resulted in dysregulated inflammatory responses, and the initiation of proliferative pathways. - endothelial sensing of dietary AHR ligands was required for optimal protection against enteric infection. - In human Endothelial cells, AHR signalling promoted quiescence and restrained activation by inflammatory mediators.
• [1.8] [#Short Chain Fatty Acid] 
  - #Butyrate and other short-chain fatty acids (SCFA), which originate from the fermentation of dietary fibers by the microbiota, can activate AhR signaling in reporter cell lines
• [#Flavonoid] - Flavonoids derived from fruits and vegetables such as quercertin and #Resveratrol have been identified as AhR ligands
• [#Indole-3-carbinole] - I3C is converted in the stomach by acid-mediated condensation into various byproducts, including high affinity AhR ligands DIM and #Indole[3,2-b] carbazole (ICZ)
• [#Indole-3-carbinole] - The main class of dietary AhR ligands is indoles, including #Indole-3-acetonitrile, #Indole-3-carbinole (I3C), 3,3’-diindolylmethane (DIM) and Indolo(3,4)bicarbazole, which are found mainly in cruciferous vegetables like #Broccoli or Brussel sprouts
• [#Indole-3-acetic acid] - #Lactobacillus can use #Tryptophan instead of #Glucose as a source of energy, and produce AhR ligands such as #Indole-3-acetic acid (IAA), #Tryptamine (TA) and 3-methyl #Indole
• [#Limosilactobacillus (Lactobacillus) reuteri] - Lactobacillus reuteri, producing the AhR ligand indole-3-aldehyde (IAld)
• [#Multiple Sclerosis] - Deficit in dietary AhR ligands increases the severity of inflammation in the central nervous system, as evidenced in the experimental autoimmune encephalomyelitis (EAE) model
• [1.9] 
  - #Tryptamine functions as a neurotransmitter that regulates intestinal motility and immune function by acting as a ligand for the aryl hydrocarbon receptor (AHR)
• [#Indole-3-acetaldehyde] - I3AA exhibits distinct inhibitory effects on regulatory T cells (Treg). I3AA alters the sensitivity of Treg cells to TGFβ signals, thereby impacting their function and ability to migrate to the gut. - AhR-dependent mechanism, with I3AA acting as an antagonist of this intracellular receptor. - PD-1 expression positively correlates with AhR activation by agonist ligands
• [#Limosilactobacillus (Lactobacillus) reuteri] [#Indole-3-acetaldehyde] - Lactobacillus reuteri is known to be a common gut-dwelling strain that possesses the ability to produce (IAld) in the I3AA-dependet pathway. - This synthesis of IAld by L. reuteri results in AhR-dependent #IL-22 production and gut protection from inflammation, indicating IAld as a beneficial bacterial-derived metabolite.
• [1.11] [#Radiofrequency field] 
  - Decreased #Indole and its metabolites (IAM) after RF may result in insufficient AHR activation, which may also contribute to RF induced #Depression-like behavior in mice
• [1.12] [#Celiac Disease] [#Tryptophan] 
  - CeD patients has a reduced capacity of converting Trp into metabolites capable of activating the AhR, leading to intestinal inflammation
• [#Limosilactobacillus (Lactobacillus) reuteri] - treating mice with #Lactobacilli strains known to produce AhR ligands such as Lactobacillus reuteri, led to increased AhR activity in the small intestine and ameliorated intestinal inflammation
• [#Tryptophan] - a Trp rich diet was able to shift the gut microbial composition of mice toward the increased abundance of bacteria able to produce AhR ligands such as #Lactobacillus and #Ruminococcus gnavus, thus reducing #Gluten immunopathology.

References Notes