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In this study, untargeted metabolomic analysis revealed marked disruption of NAD\n +<\/jats:sup>\n metabolism, accompanied by increased expression of CD38, a major NAD\n +<\/jats:sup>\n \u2010glycohydrolase, in colitis. Restoring NAD\n +<\/jats:sup>\n levels through supplementation with its precursors or pharmacological inhibition of CD38 activity effectively alleviated the pathological symptoms of colitis. Mechanistically, colitis induced a pronounced upregulation of CD38\u00a0specifically in macrophages. Myeloid\u2010specific deletion of\n Cd38\u00a0s<\/jats:italic>\n ignificantly attenuated both metabolic disturbances and inflammatory responses associated with colitis. These findings identify macrophage CD38 as a critical regulator of intestinal inflammation and highlight the CD38\/NAD\n +<\/jats:sup>\n axis as a potential therapeutic target for IBD.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n \n Altered NAD\n +<\/jats:sup>\n metabolism is closely associated with intestinal inflammation, yet the specific cellular mechanisms contributing to this decline remain to be fully elucidated.\n <\/jats:p>\n <\/jats:list-item>\n \n \n By supplementing with nicotinamide mononucleotide or inhibiting the enzyme CD38 that consumes NAD\n +<\/jats:sup>\n with drugs, the NAD\n +<\/jats:sup>\n level can be effectively restored, which can alleviate the colitis induced by dextran sulphate sodium to a certain extent.\n <\/jats:p>\n <\/jats:list-item>\n \n During intestinal inflammation, the upregulation of CD38 is predominantly driven by infiltrating macrophages.<\/jats:p>\n <\/jats:list-item>\n \n \n Myeloid\u2010specific deletion of CD38 preserves NAD\n +<\/jats:sup>\n homeostasis and ameliorates colitis, highlighting its essential role in disease progression.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Targeting macrophage CD38 establishes a key regulatory link between NAD\n +<\/jats:sup>\n metabolism and intestinal inflammation, providing a potential therapeutic strategy for inflammatory bowel diseases.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp291548","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:16:36Z","timestamp":1790738196000},"page":"8484-8500","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Macrophage\u2010derived CD38 mediates colitis through NAD\n +<\/sup>\n 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