Nicotinamide adenine dinucleotide (NAD) is an essential coenzyme associated with numerous redox reactions including energy production. NAD also serves as a substrate for ADP-ribosylation by poly(ADP-ribose) polymerase and protein deacetylation by sirtuins. NAD precursors have been reported to exhibit various beneficial effects on aging-associated diseases, such as obesity, diabetes, and Alzheimer disease in animal trials. In mammals, NAD is synthesized from niacin (nicotinamide and nicotinic acid) and tryptophan. The disease caused by niacin deficiency is pellagra featured by diarrhea, inflamed skin, and dementia. However, it is not fully understood why niacin deficiency causes Pellagra. Here we found that of deficiency of NAD synthetase (NADS) caused the villi shortening accompanied by down-regulation of transcripts regulated by beta-catenin which are associated with intestinal villi homeostasis. Furthermore, nicotinic acid rescued 5-fluorouracil-induced colitis in mice. These results suggest that the regulation of NAD metabolism plays an important role in maintaining intestinal homeostasis.