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This study aims to investigate serum amino acid metabolic profiles in patients with CAF and PFCD based on UPLC-MS\/MS. Serum samples were enrolled from newly diagnosed and treatment-na\u00efve 36 patients with active PFCD and 36 patients with CAF as controls. Clinical characteristics were systematically documented. Serum concentrations of 25 amino acids were quantitatively determined using UPLC-MS\/MS with isotopically labeled internal standards. Multivariate statistical analyses were employed to discriminate metabolic profiles between groups. Pathway enrichment analysis of differential amino acids was performed using Metabo Analyst 5.0. The PFCD cohort exhibited significantly lower total serum amino acid concentrations compared to CAF group, with 13 differentially expressed amino acids identified. Multivariate analyses revealed a significant separation trend between the two groups, eight amino acids were prioritized as candidate diagnostic biomarkers. Metabolic pathway enrichment analysis demonstrated that five pathways showed significant associations with metabolic disparities between the two groups. The proposed biomarker panel may assist in differentiating PFCD from CAF and guide individualized therapy.<\/jats:p>","DOI":"10.1038\/s41598-025-33334-7","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T04:53:55Z","timestamp":1768798435000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic profiles of amino acids in patients with crohn\u2019s disease-associated perianal fistulas and cryptoglandular anal fistulas"],"prefix":"10.1038","volume":"16","author":[{"given":"Kai","family":"Ma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cong","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feiyang","family":"Weng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yibo","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"33334_CR1","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s13287-023-03331-6","volume":"14","author":"H Wang","year":"2023","unstructured":"Wang, H. et al. 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