Authors contributed equally and share senior authorship.
Nicotinamide treatment ameliorates the course of experimental colitis mediated by enhanced neutrophil-specific antibacterial clearance
Article first published online: 25 APR 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 58, Issue 7, pages 1474–1490, July 2014
How to Cite
Bettenworth, D., Nowacki, T. M., Ross, M., Kyme, P., Schwammbach, D., Kerstiens, L., Thoennissen, G. B., Bokemeyer, C., Hengst, K., Berdel, W. E., Heidemann, J. and Thoennissen, N. H. (2014), Nicotinamide treatment ameliorates the course of experimental colitis mediated by enhanced neutrophil-specific antibacterial clearance. Mol. Nutr. Food Res., 58: 1474–1490. doi: 10.1002/mnfr.201300818
- Issue published online: 1 JUL 2014
- Article first published online: 25 APR 2014
- Manuscript Revised: 19 MAR 2014
- Manuscript Accepted: 19 MAR 2014
- Manuscript Received: 6 NOV 2013
- Innovative Medical Research
- IMF. Grant Number: BE-1-1-12-18 to DB
- Deutsche Krebshilfe e.V.. Grant Number: 109666
- Bacterial killing;
- Vitamin B3
In previous studies, we could show that the B vitamin nicotinamide (NAM) enhanced antimicrobial activity of neutrophils. Here, we assessed the effects of NAM in two models of experimental colitis.
Methods and Results
Colitis was induced in C57BL/6 mice either by oral infection with Citrobacter rodentium or by DSS (dextran sodium sulphate) administration, and animals were systemically treated with NAM. Ex vivo bacterial clearance was assessed in murine and human whole blood, as well as isolated human neutrophils. In C. rodentium-induced colitis, NAM treatment resulted in markedly decreased systemic bacterial invasion, histological damage and increased fecal clearance of C. rodentium by up to 600-fold. In contrast, NAM had no effect when administered to neutrophil-depleted mice. Ex vivo stimulation of isolated human neutrophils, as well as murine and human whole blood with NAM led to increased clearance of C. rodentium and enhanced expression of antimicrobial peptides in neutrophils. Moreover, NAM treatment significantly ameliorated the course of DSS colitis, as assessed by body weight, histological damage and myeloperoxidase activity.
Pharmacological application of NAM mediates beneficial effects in bacterial and chemically induced colitis. Future studies are needed to explore the clinical potential of NAM in the context of intestinal bacterial infections and human inflammatory bowel disease (IBD).