Inflammation blocks gut repair in Crohn’s and colitis

Dr. Lina Wehkamp began asking the question during a research stay at Penn State College of Medicine: why does an inflamed intestine fail to restore its energy supply? A German–U.S. team involving Kiel University and University Hospital Schleswig-Holstein now points to a bottleneck in the production of NAD⁺, a molecule cells use for energy metabolism, damage repair and tissue renewal.

In active Crohn’s disease and ulcerative colitis, the researchers found that production of QPRT—an enzyme involved in one of the final steps of NAD⁺ synthesis—falls. The intermediate molecule quinolinic acid accumulates, while NAD⁺ production through the tryptophan pathway drops. The result is a metabolic shortage in an intestinal lining that must constantly regenerate, particularly during inflammation.

The body does not simply stop. Using stable-isotope tracing, the team found that cells increasingly turn to alternative routes to replenish NAD⁺. Nicotinamide, a form of vitamin B3, appeared especially useful under inflammatory conditions because it can bypass the blocked section of the pathway. The experiments provide a mechanistic rationale for the ongoing ORNATUS clinical trial, which is testing locally delivered nicotinamide in ulcerative colitis; they do not yet establish that the approach works in patients.

The researchers confirmed the QPRT–NAD⁺ relationship across several independent patient cohorts and experimental models. A third study also offered initial evidence that gut bacteria may influence how tryptophan is metabolized and how efficiently NAD⁺ can be produced. That places metabolism and the microbiome alongside the immune response in the team’s picture of chronic intestinal inflammation.

So what changes in practice? Not a new prescription today, but a clearer target: restoring the intestinal lining’s energy supply could become a treatment strategy rather than treating inflammation only as an immune problem. The wider burden is visible in a separate analysis of 8,865 inflammatory bowel disease patients: 4.6% had interstitial lung disease, which was more common with ulcerative colitis than Crohn’s disease. The study’s authors say early diagnosis and screening should be considered for all patients with inflammatory bowel disease and, in resource-limited settings, perhaps focus on ulcerative colitis.