{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:19:55Z","timestamp":1792030795818,"version":"4.4.0"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2021YFC2301801"],"award-info":[{"award-number":["2021YFC2301801"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Elderly individuals infected with SARS-CoV-2 are at higher risk of developing cytokine storms and severe outcomes, yet specific biomarkers remain unclear. In this study, we investigated the alteration of primary bile acid metabolism in elderly patients with severe COVID-19 using untargeted metabolomics (n = 31), followed by targeted metabolomics to compare patients with disease progression (n = 16) to those without (n = 48). Significant reductions in chenodeoxycholic acid (CDCA) and glycochenodeoxycholic acid (GCDCA) levels were identified in severe cases, with GCDCA levels at admission correlating strongly with peak inflammatory markers. In vitro, CDCA, GCDCA, and their receptors, Farnesoid X Receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5), effectively inhibited the inflammatory response induced by SARS-CoV-2. NOD-like receptor pathway, activated by SARS-CoV-2, may modulate inflammatory cytokines under the treatment of CDCA, GCDCA, and TGR5. CDCA and GCDCA levels at admission predicted disease progression, suggesting their potential as biomarkers for severe COVID-19 in the elderly and highlighting their regulatory role in inflammation, pointing to new therapeutic avenues.<\/jats:p>","DOI":"10.3390\/biom15070943","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T07:55:43Z","timestamp":1751442943000},"page":"943","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Significant Reduction of Chenodeoxycholic Acid and Glycochenodeoxycholic Acid in the Elderly with Severe COVID-19"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9311-4020","authenticated-orcid":false,"given":"Shiyang","family":"Liu","sequence":"first","affiliation":[{"name":"Chinese People\u2019s Liberation Army (PLA) Medical School, Beijing 100853, China"},{"name":"Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100073, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Xu","sequence":"additional","affiliation":[{"name":"Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100073, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Tu","sequence":"additional","affiliation":[{"name":"Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100073, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqing","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, The Seventh Medical Center, College of Pulmonary and Critical Care Medicine of The Eighth Medical Center, Chinese PLA General Hospital, Beijing 100007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Li","sequence":"additional","affiliation":[{"name":"Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100073, China"},{"name":"Yu-Yue Pathology Scientific Research Center, Chongqing 401329, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Huang","sequence":"additional","affiliation":[{"name":"Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100073, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yuan","sequence":"additional","affiliation":[{"name":"Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100073, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengdong","family":"Luo","sequence":"additional","affiliation":[{"name":"Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100073, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100073, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Yang","sequence":"additional","affiliation":[{"name":"Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100073, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlian","family":"Yang","sequence":"additional","affiliation":[{"name":"Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100073, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, The Seventh Medical Center, College of Pulmonary and Critical Care Medicine of The Eighth Medical Center, Chinese PLA General Hospital, Beijing 100007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1683-4785","authenticated-orcid":false,"given":"Weiwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Senior Department of 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