{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:17:08Z","timestamp":1791253028542,"version":"4.1.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":31,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BMBF iTREAT"},{"name":"DFG Cluster of excellence"},{"name":"EU project miGut-Health","award":["#2019_A09"],"award-info":[{"award-number":["#2019_A09"]}]},{"name":"EKFS Clinician Scientist Professorship","award":["2020_EKCS.11"],"award-info":[{"award-number":["2020_EKCS.11"]}]},{"DOI":"10.13039\/501100002347","name":"BMBF","doi-asserted-by":"publisher","award":["Try-IBD\u2019 01ZX1915A"],"award-info":[{"award-number":["Try-IBD\u2019 01ZX1915A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"BMBF","doi-asserted-by":"publisher","award":["01ZX2215"],"award-info":[{"award-number":["01ZX2215"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004807","name":"DFG","doi-asserted-by":"publisher","award":["RU5042"],"award-info":[{"award-number":["RU5042"]}],"id":[{"id":"10.13039\/100004807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008662","name":"Joachim Herz Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008662","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["T32GM108563"],"award-info":[{"award-number":["T32GM108563"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Howard Hughes Medical Institute Hanna H. Gray Fellows Program Faculty Phase","award":["GT15655"],"award-info":[{"award-number":["GT15655"]}]},{"name":"Burroughs Welcome Fund PDEP","award":["1022604"],"award-info":[{"award-number":["1022604"]}]},{"name":"ECCO Multiyear Research Grant 2021"},{"name":"Clinical Research Fund"},{"name":"University Hospitals Leuven and the Research Council at the KU Leuven"},{"name":"Innovative Medicines Initiative 2 Joint Undertaking","award":["853995"],"award-info":[{"award-number":["853995"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program and EFPIA"},{"name":"ERC Advanced grant \u2018MADMICs\u2019"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Inflammatory bowel disease (IBD) is associated with energy deficiency and perturbed metabolism of the essential amino acid tryptophan (Trp).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We aimed to determine whether excessive Trp degradation fuels or compensates for inflammation through de novo nicotinamide adenine dinucleotide (NAD+) synthesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A prospective systems medicine approach (metabolomics, transcriptomics) was employed longitudinally in patients with advanced IBD therapy. Findings were validated with targeted Trp metabolomics in experimental colitis and in vitro in fibroblasts, intestinal epithelial cells (IECs), and peripheral blood mononuclear cells (PBMCs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Active IBD is marked by enhanced Trp degradation driven by inflammatory cytokines through the JAK\/STAT pathway. Trp catabolism results in accumulation of quinolinic acid (QA) and NAD\u2009+\u2009depletion due to reduced expression of QPRT, the enzyme converting QA to NAD+. QPRT knockdown enhances inflammation, while NAD\u2009+\u2009precursor supplementation (e.g. nicotinamide riboside [NR]) restores cellular energy and reduces inflammation in vitro and in dextran sodium sulfate (DSS)-induced colitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A metabolic bottleneck at QPRT prevents efficient NAD+ synthesis from Trp in IBD, sustaining inflammation. Restoring NAD\u2009+\u2009is a promising therapeutic strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjag043","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T12:58:20Z","timestamp":1773838700000},"source":"Crossref","is-referenced-by-count":4,"title":["A metabolic constraint in\n                    <i>de novo<\/i>\n                    NAD+ synthesis drives mucosal inflammation in IBD"],"prefix":"10.1093","volume":"20","author":[{"given":"Lina","family":"Wehkamp","sequence":"first","affiliation":[{"name":"Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein , Kiel, 24105,","place":["Germany"]},{"name":"Department of Internal Medicine I, Christian-Albrechts-University and University Hospital Schleswig-Holstein , Kiel, 24105,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1950-399X","authenticated-orcid":false,"given":"Danielle M M","family":"Harris","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein , Kiel, 24105,","place":["Germany"]},{"name":"Department of Internal Medicine I, Christian-Albrechts-University and University Hospital Schleswig-Holstein , Kiel, 24105,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na-mi","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein , Kiel, 24105,","place":["Germany"]},{"name":"Department of Internal Medicine I, Christian-Albrechts-University and University Hospital Schleswig-Holstein , Kiel, 24105,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abrar I","family":"Alsaadi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University , University Park, PA, 16802,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qicong","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein , Kiel, 24105,","place":["Germany"]},{"name":"Department of Internal Medicine I, Christian-Albrechts-University and University Hospital Schleswig-Holstein , Kiel, 24105,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mhmd","family":"Oumari","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Christian-Albrechts-University and 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10117,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timon","family":"Adolph","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Gastroenterology, Hepatology & Metabolism, Medical University Innsbruck , Innsbruck, 6020,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"D\u2019Haens","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers , Amsterdam, 1081HZ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Kaleta","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, Christian-Albrechts-University and University Hospital Schleswig-Holstein , Kiel, 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