{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:37:25Z","timestamp":1788460645389,"version":"build-2803163510"},"reference-count":76,"publisher":"American Society of Hematology","issue":"13","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,3,26]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Chronic granulomatous disease (CGD) is an inborn error of immunity associated with a 50% prevalence of inflammatory bowel disease (IBD) for which current treatments are suboptimal due to the increased risk of infections in this population. CGD results from defects in the nicotinamide adenine dinucleotide phosphate oxidase 2 complex, leading to minimal or absent phagocyte-derived reactive oxygen species production. Patients with CGD present with recurrent infections and severe inflammatory complications, especially in the gut. These inflammatory complications have been associated with the increased systemic activation of the nucleotide-binding domain and leucine-rich-repeat\u2013containing protein 3 (NLRP3) inflammasome and dysregulation of the T-cell compartment. However, the role of the NLRP3 inflammasome at the intestinal barrier and whether it can be targeted to treat CGD-associated IBD (CGD-IBD) remain unclear. \u03b2-Hydroxybutyrate (\u03b2HB), a ketone body produced during fasting or adherence to a ketogenic diet, can inhibit the NLRP3 inflammasome and restore T-cell balance. In this preclinical study, we demonstrated that a ketogenic diet significantly improves colitis in CGD mice, to a greater extent than in wild-type mice, by reducing NLRP3 inflammasome activity, altering the microbiota, and inducing tolerogenic immune populations at the intestinal mucosal barrier. We also showed that \u03b2HB supplementation could significantly improve colitis in CGD mice and decrease systemic inflammation. We further confirmed that, in the blood cells of humans with CGD, \u03b2HB effectively reduces the levels of cytokines associated with inflammasome activation. In conclusion, our study identified that NLRP3 inflammasome blockade using a ketogenic diet or \u03b2HB supplementation is a potential novel and safer treatment for CGD-IBD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025029676","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T03:53:26Z","timestamp":1764647606000},"page":"1456-1469","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":3,"title":["NLRP3 inflammasome blockade treats intestinal inflammation associated with chronic granulomatous disease"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7511-4429","authenticated-orcid":false,"given":"Emma","family":"Darbinian","sequence":"first","affiliation":[{"name":"1Center for Immunity, Inflammation and Infectious Diseases, Montreal Clinical Research Institute, Montreal, QC, Canada"},{"name":"2Molecular Biology Program, Faculty of 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