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Our current study aims to explore the underlying mechanisms by assessing the intermediated effects of circulating short-chain organic acids (SCOAs) on this association. Methods: Depressive symptoms were screened by the 30-item Geriatric Depression Scale (GDS-30). Urinary concentrations of antibiotics and serum SCOAs were measured using a liquid chromatography\u2013mass spectrometry method. Results: Increased exposure to sulfadiazine, azithromycin, tetracyclines, or veterinary antibiotics (VAs) was positively associated with GDS-30 scores. Tetracycline reduced levels of caproic acid, iso-butyric acid, and iso-caproic acid (iso-CA), with iso-CA concentration inversely correlating with GDS-30 scores, while \u03b2-hydroxybutyric acids showed a positive correlation. The mediating effect of serum iso-CA on the association between depression and ofloxacin, with a mediating effect of 25.3%, and the association between depression and tetracycline, with a mediating effect of 46.3%, were both statistically significant, indicating partial mediation. Conclusions: Antibiotics may affect the levels of SCOAs in older adults and could potentially contribute to depressive symptoms by influencing alterations in serum iso-CA levels.<\/jats:p>","DOI":"10.3390\/metabo14120689","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T10:11:47Z","timestamp":1733739107000},"page":"689","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Metabolic Alterations of Short-Chain Organic Acids in the Elderly Link Antibiotic Exposure with the Risk for Depression"],"prefix":"10.3390","volume":"14","author":[{"given":"Shujing","family":"Sun","sequence":"first","affiliation":[{"name":"School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China"},{"name":"Center for Big Data and Population Health of IHM, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Kong","sequence":"additional","affiliation":[{"name":"School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China"},{"name":"Center for Big Data and Population Health of IHM, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangting","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China"},{"name":"Center for Big Data and Population Health of IHM, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Scientific Research, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglong","family":"Geng","sequence":"additional","affiliation":[{"name":"School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China"},{"name":"Center for Big Data and Population Health of IHM, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China"},{"name":"Key Laboratory of Population Health Across Life Cycle, Ministry of Education of the People\u2019s Republic of China, No. 81 Meishan Road, Hefei 230032, China"},{"name":"Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course, No. 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjuan","family":"Cao","sequence":"additional","affiliation":[{"name":"Lu\u2019an Center of Disease Control and Prevention, Lu\u2019an 237000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyong","family":"Tao","sequence":"additional","affiliation":[{"name":"School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China"},{"name":"Center for Big Data and Population Health of IHM, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangbiao","family":"Tao","sequence":"additional","affiliation":[{"name":"School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China"},{"name":"Center for Big Data and Population Health of IHM, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China"},{"name":"Key Laboratory of Population Health Across Life Cycle, Ministry of Education of the People\u2019s Republic of China, No. 81 Meishan Road, Hefei 230032, China"},{"name":"Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course, No. 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4492-9474","authenticated-orcid":false,"given":"Kaiyong","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China"},{"name":"Center for Big Data and Population Health of IHM, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China"},{"name":"Key Laboratory of Population Health Across Life Cycle, Ministry of Education of the People\u2019s Republic of China, No. 81 Meishan Road, Hefei 230032, China"},{"name":"Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course, No. 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1257\/jep.37.2.179","article-title":"Depression and Loneliness among the Elderly in Low- and Middle-Income Countries","volume":"37","author":"Banerjee","year":"2023","journal-title":"J. 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