{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:19:14Z","timestamp":1792181954867,"version":"4.4.0"},"reference-count":75,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,26]],"date-time":"2022-11-26T00:00:00Z","timestamp":1669420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Millenium Pharmaceutical Research"},{"name":"MWAC Analytical Centre Research Grant UNSW"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The epithelial barrier\u2019s primary role is to protect against entry of foreign and pathogenic elements. Both COVID-19 and Inflammatory Bowel Disease (IBD) show commonalities in symptoms and treatment with sensitization of the epithelial barrier inviting an immune response. In this study we use a multi-omics strategy to identify a common signature of immune disease that may be able to predict for more severe patient outcomes. Global proteomic approaches were applied to transcriptome and proteome. Further semi- and relative- quantitative targeted mass spectrometry methods were developed to substantiate the proteomic and metabolomics changes in nasal swabs from healthy, COVID-19 (24 h and 3 weeks post infection); serums from Crohn\u2019s disease patients (scored for epithelial leak), terminal ileum tissue biopsies (patient matched inflamed and non-inflamed regions, and controls). We found that the tryptophan\/kynurenine metabolism pathway is a \u2018hub\u2019 regulator of canonical and non-canonical transcription, macrophage release of cytokines and significant changes in the immune and metabolic status with increasing severity and disease course. Significantly modified pathways include stress response regulator EIF2 signaling (p = 1 \u00d7 10\u22123); energy metabolism, KYNU (p = 4 \u00d7 10\u22124), WARS (p = 1 \u00d7 10\u22127); inflammation, and IDO activity (p = 1 \u00d7 10\u22126). Heightened levels of PARP1, WARS and KYNU are predictive at the acute stage of infection for resilience, while in contrast, levels remained high and are predictive of persistent and more severe outcomes in COVID disease. Generation of a targeted marker profile showed these changes in immune disease underlay resolution of epithelial barrier function and have the potential to define disease trajectory and more severe patient outcomes.<\/jats:p>","DOI":"10.3390\/ijms232314776","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T01:58:46Z","timestamp":1669600726000},"page":"14776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Tryptophan Metabolism \u2018Hub\u2019 Gene Expression Associates with Increased Inflammation and Severe Disease Outcomes in COVID-19 Infection and Inflammatory Bowel Disease"],"prefix":"10.3390","volume":"23","author":[{"given":"Sonia","family":"Bustamante","sequence":"first","affiliation":[{"name":"Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, The University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8832-8200","authenticated-orcid":false,"given":"Yunki","family":"Yau","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Concord Repatriation General Hospital, Sydney, NSW 2139, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6844-2559","authenticated-orcid":false,"given":"Victoria","family":"Boys","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, Faculty of Medicine, The University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Concord Repatriation General Hospital, Sydney, NSW 2139, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudarshan","family":"Paramsothy","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Concord Repatriation General Hospital, Sydney, NSW 2139, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aviv","family":"Pudipeddi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Concord Repatriation General Hospital, Sydney, NSW 2139, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupert W.","family":"Leong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Concord Repatriation General Hospital, Sydney, NSW 2139, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5338-0869","authenticated-orcid":false,"given":"Valerie C.","family":"Wasinger","sequence":"additional","affiliation":[{"name":"Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, The University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1001\/jama.2020.6775","article-title":"Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area","volume":"323","author":"Richardson","year":"2020","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e048391","DOI":"10.1136\/bmjopen-2020-048391","article-title":"Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome: A prospective, community-based study","volume":"11","author":"Dennis","year":"2021","journal-title":"BMJ Open"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.cell.2020.02.021","article-title":"Stressful Beginnings with Long-Term Consequences","volume":"180","author":"Consiglio","year":"2020","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41586-019-1326-9","article-title":"TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection","volume":"571","author":"Alfei","year":"2019","journal-title":"Nature"},{"key":"ref_5","first-page":"100193","article-title":"Whole of population-based cohort study of recovery time from COVID-19 in New South Wales Australia","volume":"12","author":"Liu","year":"2021","journal-title":"Lancet Reg. 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