# Metabolic profiles of amino acids in patients with crohn’s disease-associated perianal fistulas and cryptoglandular anal fistulas

**Authors:** Kai Ma, Cong Hu, Yi Fu, Yu Liu, Feiyang Weng, Yibo Yao, Chen Wang

PMC · DOI: 10.1038/s41598-025-33334-7 · 2026-01-19

## TL;DR

This study compares amino acid levels in two types of anal fistulas to identify potential biomarkers for diagnosis and treatment.

## Contribution

The study identifies distinct amino acid metabolic profiles that could help differentiate Crohn’s disease-associated fistulas from cryptoglandular fistulas.

## Key findings

- PFCD patients had significantly lower total serum amino acid concentrations than CAF patients.
- 13 amino acids were found to be differentially expressed between the two groups.
- Eight amino acids were identified as potential diagnostic biomarkers.

## Abstract

Crohn’s disease-associated perianal fistulas (PFCD) and Cryptoglandular anal fistulas (CAF) are two types of fistulas with similar clinical manifestations but distinct etiologies and therapeutic strategies. 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-naïve 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.

The online version contains supplementary material available at 10.1038/s41598-025-33334-7.

## Linked entities

- **Diseases:** Crohn’s disease (MONDO:0005011)

## Full-text entities

- **Genes:** CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, VIP (vasoactive intestinal peptide) [NCBI Gene 7432] {aka PHM27}
- **Diseases:** liver or kidney dysfunction (MESH:D051437), anal strictures (MESH:D003251), immune dysregulation (OMIM:614878), Sar (MESH:C537236), fistula (MESH:D005402), CD (MESH:D003424), tissue injury (MESH:D017695), infection (MESH:D007239), nutrient malabsorption (MESH:D008286), muscle wasting (MESH:D009133), pilonidal disease (MESH:D010864), IBD (MESH:D015212), infectious gastroenteritis (MESH:D005759), HIV infection (MESH:D015658), malignancy (MESH:D009369), trauma (MESH:D014947), Nutritional deficiencies (MESH:D044342), gland (MESH:D000307), intestinal dysbiosis (MESH:D064806), Metabolic disturbance (MESH:D024821), amino acid deficiency (MESH:D000592), renal (MESH:D006030), abscess (MESH:D000038), chronic inflammation (MESH:D007249), fecal incontinence (MESH:D005242), anorectal pain (MESH:D010146), Perianal Disease (MESH:D000694), CAF (MESH:D012003)
- **Chemicals:** kynurenine (MESH:D007737), Amino acid (MESH:D000596), Trp (MESH:D014364), HCl (MESH:D006851), Leu (MESH:D007930), formic acid (MESH:C030544), nitrogen (MESH:D009584), Val (MESH:D014633), Phe (MESH:D010649), NO (MESH:D009614), aromatic amino acids (MESH:D024322), polyamines (MESH:D011073), histamine (MESH:D006632), GSH (MESH:D005978), Glu (MESH:D018698), Gly (MESH:D005998), BCAAs (MESH:D000597), sulfur (MESH:D013455), Cys (MESH:D003545), acetonitrile (MESH:C032159), Met (MESH:D008715), Amino (-), nitric oxide (MESH:D009569), catecholamines (MESH:D002395), Gln (MESH:D005973), Arg (MESH:D001120), Asp (MESH:D001224), Tyr (MESH:D014443), urea (MESH:D014508), Thr (MESH:D013912), oxygen (MESH:D010100), Lys (MESH:D008239), Ser (MESH:D012694), Sar (MESH:D012521), Ile (MESH:D007532), carbon (MESH:D002244), 2-aminoisobutyric acid (MESH:C100049), water (MESH:D014867), His (MESH:D006639), Cit (MESH:D002956), Asn (MESH:D001216), Ala (MESH:D000409), folate (MESH:D005492), Pro (MESH:D011392), hydrogen (MESH:D006859), Orn (MESH:D009952), tricarboxylic acid (MESH:D014233)
- **Species:** Human immunodeficiency virus 1 (no rank) [taxon 11676], Human immunodeficiency virus (species) [taxon 12721], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** Trp/His, R2Y, R2, L2, Q2, Phe/Tyr, A2

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12835150/full.md

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Source: https://tomesphere.com/paper/PMC12835150