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While previous research has elucidated the intricate dynamics of the gut\u2013brain axis, the interplay between serotonin pathway metabolites and gut microbiota in individuals undergoing hemodialysis remains largely unexplored. Therefore, this study aimed to investigate gut microbiota composition corresponding to serotonin pathway metabolite levels among patients with hemodialysis. A total of 85 patients undergoing hemodialysis were selected. Their gut microbiota was analyzed using shotgun metagenomic sequencing profiling. The serotonin pathway metabolites, including 5-hydroxytryptophan (5-HTP), serotonin, 5-methoxytryptophan (5-MTP), 5-methoxytryptamine, melatonin, and 6-hydroxymelatonin, were analyzed with the liquid chromatograph\u2013tandem mass spectrometer. The robust linear discriminant analysis Effect Size (LEfSe) was employed to reveal the gut microbiota signature according to levels of serotonin pathway metabolites. A significant \u03b2-diversity difference in 5-Methoxytryptamine (p = 0.037) was found, while no variance in \u03b1-diversity was detected. Using LefSe analysis, we identified an enriched Tannerellaceae family in the high-hydroxytryptophan (5-HTP) group, the Odoribacteraceae family in the high-serotonin group, the Eubacteriales order in the high-5-methoxytryptophan (5-MTP) group, the Prevotella copri species in the high-5-Methoxytryptamine group, and the Clostridium genus in the high-melatonin group. In contrast, an enriched Clostridiaceae family in the low-5-HTP group, the Clostridiaceae family in the low-serotonin group, and the Bacteroides ovatus species in the low-5-MTP group were found. Distinct gut microbiota signatures linked to serotonin pathway metabolites were identified in patients undergoing hemodialysis. These findings provide insights for future gut\u2013brain axis research and may guide methods to modulate gut microbiota to influence serotonin metabolites.<\/jats:p>","DOI":"10.3390\/ijms262110463","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T13:59:36Z","timestamp":1761659976000},"page":"10463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of Gut Microbiome Signatures Associated with Serotonin Pathway in Tryptophan Metabolism of Patients Undergoing Hemodialysis"],"prefix":"10.3390","volume":"26","author":[{"given":"Tien-Hsiang","family":"Kuo","sequence":"first","affiliation":[{"name":"School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1021-8161","authenticated-orcid":false,"given":"Ping-Hsun","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Center for Big Data Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Biomedical Artificial Intelligence Academy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1290-0850","authenticated-orcid":false,"given":"Po-Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung 80424, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5077-191X","authenticated-orcid":false,"given":"Yun-Shiuan","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2988-8598","authenticated-orcid":false,"given":"Chi-Jung","family":"Tai","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Family Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Family Medicine, Pingtung Hospital, Ministry of Health and Welfare, Pingtung 90003, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0244-7685","authenticated-orcid":false,"given":"Mei-Chuan","family":"Kuo","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Wen","family":"Chiu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5833-0040","authenticated-orcid":false,"given":"Yi-Ting","family":"Lin","sequence":"additional","affiliation":[{"name":"Center for Big Data Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.7150\/ijms.82667","article-title":"Role of the gut microbiota and their metabolites in hemodialysis patients","volume":"20","author":"Chao","year":"2023","journal-title":"Int. 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