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Mol. Sci.","IJMS"],"abstract":"<jats:p>Biomarkers with potential for use in clinical diagnosis have been widely studied using biochemical techniques. In particular, endogenous and exogenous metabolites have been targeted in clinical settings. Both types of metabolites are either unmetabolized, metabolized with human enzymes, or metabolized with host-resident bacterial enzymes. In standard clinical chemistry, a specimen must be collected following overnight fasting to minimize the effect of dietary input and the subsequent host and microbial metabolism. Current technology allows the detection of nanomolar concentrations of exogenously derived biomarkers, and these ultra-high sensitivity assays have increased the use of trace amounts of such biomarkers. This narrative review explores how the gut\u2013liver\u2013kidney axis modulates disease manifestation and biomarker accumulations in chronic disorders and inborn errors of metabolism in neonates.<\/jats:p>","DOI":"10.3390\/ijms27188201","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:32:01Z","timestamp":1789468321000},"page":"8201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of the Gut\u2013Liver\u2013Kidney Axis in Disease Manifestation and Biomarker Alterations"],"prefix":"10.3390","volume":"27","author":[{"given":"Ryuichi","family":"Mashima","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1386-2705","authenticated-orcid":false,"given":"Nobuyuki","family":"Ishige","sequence":"additional","affiliation":[{"name":"Division of Newborn Screening, Tokyo Health Service Association, 1-2-59 Ichigaya-Sadohara, Shinjuku 162-8460, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"D622","DOI":"10.1093\/nar\/gkab1062","article-title":"HMDB 5.0: The Human Metabolome Database for 2022","volume":"50","author":"Wishart","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.bbalip.2017.05.006","article-title":"The importance of bioinformatics for connecting data-driven lipidomics and biological insights","volume":"1862","author":"Tsugawa","year":"2017","journal-title":"Biochim. 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