{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T09:34:33Z","timestamp":1768815273279,"version":"3.49.0"},"reference-count":48,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01HL158779"],"award-info":[{"award-number":["R01HL158779"]}]},{"name":"NIH","award":["R01AI172873"],"award-info":[{"award-number":["R01AI172873"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is intricately related to the reprogramming of host metabolism. However, existing studies have mainly focused on peripheral blood samples and barely identified specific metabolites that are critically involved in the pathology of coronavirus disease 2019 (COVID-19). In the current small-scale study, we performed metabolic profiling in plasma (n = 61) and paired bronchoalveolar lavage fluid (BALF) samples (n = 20) using parallel two-dimensional liquid chromatography\u2013mass spectrometry (2DLC-MS). In addition, we studied how an identified metabolite regulates the immunopathogenesis of COVID-19. The results unveiled distinct metabolome changes between healthy donors, and moderate and severe patients in both plasma and BALF, indicating that locations and disease severity play critical roles in COVID-19 metabolic alteration. Notably, a vital metabolite, indoxyl sulfate, was found to be elevated in both the plasma and BALF of severe COVID-19 patients. Indoxyl sulfate selectively induced TNF-\u03b1 production, reduced co-stimulatory signals, and enhanced apoptosis in human monocytes. Moreover, its levels negatively correlated with the strength of co-stimulatory signals and antigen presentation capability in monocytes of COVID-19 patients. Collectively, our findings suggest that the levels of indoxyl sulfate could potentially serve as a functional biomarker to monitor COVID-19 disease progression and guide more individualized treatment for COVID-19 patients.<\/jats:p>","DOI":"10.3390\/cells14040256","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T09:36:05Z","timestamp":1739266565000},"page":"256","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolomics Profiling Reveals Critical Roles of Indoxyl Sulfate in the Regulation of Innate Monocytes in COVID-19"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0428-814X","authenticated-orcid":false,"given":"Liqing","family":"He","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunke","family":"Wang","sequence":"additional","affiliation":[{"name":"Immuno-Oncology Program, Brown Cancer Center, Division of Immunotherapy, MD Department of Surgery, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Morrissey","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne E.","family":"Geller","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoling","family":"Hu","sequence":"additional","affiliation":[{"name":"Immuno-Oncology Program, Brown Cancer Center, Division of Immunotherapy, MD Department of Surgery, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7178-8961","authenticated-orcid":false,"given":"Raobo","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xipeng","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huang-ge","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7816-3286","authenticated-orcid":false,"given":"Kenneth","family":"McLeish","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4794-8400","authenticated-orcid":false,"given":"Jiapeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, University of Louisville Hospital, Louisville, KY 40292, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1102-6313","authenticated-orcid":false,"given":"Xiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2922-422X","authenticated-orcid":false,"given":"Jun","family":"Yan","sequence":"additional","affiliation":[{"name":"Immuno-Oncology Program, Brown Cancer Center, Division of Immunotherapy, MD Department of Surgery, University of Louisville, Louisville, KY 40292, USA"},{"name":"Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e966","DOI":"10.1016\/S2468-2667(22)00223-7","article-title":"COVID-19 mortality and deprivation: Pandemic, syndemic, and endemic health inequalities","volume":"7","author":"McGowan","year":"2022","journal-title":"Lancet Public Health"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Onoja, A., von Gerichten, J., Lewis, H.M., Bailey, M.J., Skene, D.J., Geifman, N., and Spick, M. 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