Microbiome & Chronic Diseases

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kynurenine {90000122}

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- In humans, kynurenine is primarily synthesised endogenously from tryptophan.
- The kynurenine pathway produces several neuroactive products within the brain – both neuroprotective and neurotoxic
- Patients with Alzheimer’s disease (AD) will have lower levels of tryptophan and kynurenic acid and increased levels of quinolinic acid in their plasma.
- Patients with Parkinson’s disease (PD) will have increased ratios of kynurenic acid and kynurenic acid/kynurenine, with lower ratios of quinolinic acid and quinolinic acid/kynurenine acid.
- Kynurenine can also limit the tryptophan available for serotonin synthesis in the brain, though most serotonin is produced before dietary tryptophan is absorbed into the circulatory system in the intestine.
- Intestinal microbiota affect the kynurenine pathway by influencing the absorption of tryptophan before it reaches the liver, where most kynurenine synthesis takes place.
- In the intestinal lumen, bacteria can convert tryptophan to indole, sending dietary tryptophan to the indole pathway.
- Indole itself serves as a signalling molecule for bacteria such as E. coli and can send warning signals for signs of inflammation in the gut.

Shared Notes

  • [1.4
    - The kynurenine metabolites can participate in numerous neurodegenerative disorders (Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, and Parkinson disease) or other diseases such as AIDS, cancer, cardiovascular diseases, inflammation, and irritable bowel syndrome.
  • [1.5
    - Kynurenine—a tryptophan metabolite that blocks antitumour immunity—inhibits T cell proliferation in a manner that can be rescued by BH4.
  • [1.6
    - The blood–brain barrier allows the access of kynurenines.
    - changes in KYN and SCFAs brain levels may underlay the development of mood disorders and anxiety, while KYN may be involved in visceral hypersensitivity by modulating visceral pain along the gut–brain axis.
  • [1.1
    - Greater abundance of Ruminococcus, at genus level > related to higher risk of ALS.
    - Kynurenine > risk factor of ALS.
  • [1.7
    - kynurenic acid > signaling through GPR35, expressed on IECs and immune cells > immunoregulatory effects > protects the intestine.
    - Gut-derived kynurenines and 5-HT are additionally implicated in the pathogenesis of chronic inflammatory, metabolic and neuropsychiatric diseases.
  • [1.2
    - Tryptophan > Excessive Kyn levels in the tumor microenvironment is one of the adaptive mechanism for the tumors to escape immune surveillance and metastasize. Most individuals with cancer, including hepatocellular carcinoma, CRC, kidney cancer, lung cancer often exhibit increased Kyn levels and decreased serum Trp levels, or increased kyn/Trp ratio.
  • [1.3
    - Metabolomics revealed elevated plasma kynurenine at G15/19 in all three mouse strains. IDO1, the rate limiting enzyme for kynurenine production, had increased intestinal expression at G15, which was associated with mild systemic and gut inflammation.
  • [1.9
    - The enhanced conversion of tryptophan into kynurenine is associated with MS occurrence and worse outcomes.
  • -IBS > the level of neuroprotective kynurenic acid (KynA) and the ratio of KynA/Kyn were reduced
  • [1.11
    - dimethylglycine, imidazole propionate, tryptophan, kynurenine and indolelactate associated with increased risk of T2D
  • - SCFAs, serotonin, kynurenine, indole and its derivatives, and tryptamine, can bridge the gut and nervous system.
  • - kynurenine and indole derivatives might be associated with neurogenic depression

Common References