In Crohn's disease and ulcerative colitis, inflammation blocks its own healing

Inflammation in Crohn's disease and ulcerative colitis disrupts intestinal healing by blocking the production of a critical molecule needed for cellular energy metabolism. Researchers at Kiel University and Penn State College of Medicine have discovered that chronic inflammation interferes with the synthesis of nicotinamide adenine dinucleotide (NAD+), a molecule vital to cell function and tissue repair.

NAD+ is primarily produced from the amino acid tryptophan, but this pathway is disrupted during inflammation. The enzyme quinolinate phosphoribosyltransferase (QPRT) is reduced in activity during active intestinal inflammation, leading to a buildup of quinolinic acid and a drop in NAD+ production. This metabolic bottleneck hinders the intestinal lining's ability to regenerate, causing persistent inflammation.

In response to NAD+ depletion, the body activates alternative metabolic routes, such as increased use of nicotinamide (a form of vitamin B3) to produce more NAD+. These findings, published in the Journal of Crohn's and Colitis and Cell Reports, suggest new therapeutic strategies, like locally delivered nicotinamide, could potentially support intestinal repair in inflammatory bowel diseases.

The research also indicates the gut microbiome may influence NAD+ production through tryptophan metabolism, adding another layer to the metabolic network of these conditions.