In chronic inflammatory bowel diseases (CED), an inflammation remains in the intestinal mucosa, even though the immune system tries to bring it under control. In this process, a disturbed metabolism of the essential amino acid tryptophan, which leads to an energy shortage in important immune cells, …
In chronic inflammatory bowel diseases (CED), an inflammation remains in the intestinal mucosa, even though the immune system tries to bring it under control. In this process, a disturbed metabolism of the essential amino acid tryptophan, which leads to an energy shortage in important immune cells, seems to play a role. This has been found by a German-American research team involved in the Excellence Cluster PMI - Precision Medicine for Chronic Inflammatory Diseases at Kiel University (CAU) and published in three closely related studies. In a study published in the 'Journal of Crohn's and Colitis', a team led by Dr. Lina Wehkamp from CAU showed how chronic inflammation disrupts the formation of the energy carrier Nicotinamidadenindinukleotid (NAD⁺). This plays a central role in energy gain and tissue regeneration. The intestinal mucosa, which is a very active tissue that must constantly renew itself, relies on reliable supply. This is especially true when it is inflamed. 'Actually, the body tries to repair the damaged mucosa during an inflammation. For this, it needs large amounts of energy,' explains Wehkamp in a press release from PMI. Instead, the production of the important energy carrier is hindered. To find out why, researchers combined patient data, cell experiments and mouse models and examined them for tryptophan and NAD⁺ metabolism. In this process, a bottleneck was found: inflammatory mediators promote the breakdown of tryptophan via the so-called kynurenine pathway, which is normally used to produce NAD⁺. At the same time, an active inflammation suppresses the enzyme Chinolinat-Phosphoribosyltransferase (QPRT), which converts the intermediate product quinolinate into NAD⁺. The acid accumulates, the NAD⁺ levels drop and the intestinal mucosa can regenerate worse due to the energy shortage. The inflammation thus holds itself upright. The researchers show for the first time that QPRT is also reduced in inflammatory bowel diseases. In cell and animal models, the addition of NAD⁺ precursors, nicotinamide and nicotinamide riboside, improved energy supply and dampened inflammatory reactions.
