{
  "abstract": "Background 5-Aminosalicylic acid (5-ASA) remains the first-line therapy for mild-to-moderate ulcerative colitis (UC). However, only half of the patients exhibit a good response. The mechanisms underlying inter-individual variation in 5-ASA efficacy remain unclear. This study integrated plasma proteomics with mechanistic validation to elucidate the role and underlying mechanisms of sulfotransferase family 1A member 1 (ST1A1, gene name SULT1A1) in modulating 5-ASA therapeutic efficacy.Methods Baseline serum from 36 UC patients (18 responders and 18 non-responders after 5-ASA treatment) were analyzed using Olink proteomics, and verified by ELISA, immunohistochemistry, and western blot. Functional studies were performed in NCM460 cells through siRNA-mediated knockdown or ­plasmid overexpression and the stimulation with dextran sulfate sodium (DSS) or lipopolysaccharide (LPS). Intracellular 5-ASA was quantified by high-performance liquid chromatography. Transcriptome sequencing and GSVA analysis identified differentially enriched pathways. ST1A1-targeted adeno-associated virus (AAV) intestinal epithelial Sult1a1-knockdown mouse model was established to assess ST1A1 function in vivo.Results Olink proteomic profiling identified ST1A1 as significantly elevated in 5-ASA-ineffective patients ( IDDF2026-ABS-0182 Figure 1(A)), which was subsequently confirmed by its upregulation in plasma and colonic mucosa in an independent validation cohort (IDDF2026-ABS-0182 Figure 1(B-D)). In vitro, SULT1A1 knockdown could ameliorate both DSS- and LPS-induced inflammatory cytokine expression and the destruction of tight junction proteins, whereas overexpression had the opposite effects. Mechanistically, ST1A1 activated the EGFR-MAPK axis, suppressed 5-ASA epithelial uptake transporter organic anion transporting polypeptide 1B3, and induced 5-ASA metabolic enzyme N-acetyltransferase 1, thereby reducing intracellular 5-ASA level. In vivo, Sult1a1 knockdown alleviated mouse DSS colitis, increased the colonic levels of 5-ASA and thus enhanced the anti-inflammatory effect of 5-ASA (IDDF2026-ABS-0182 Figure 1(E-I)).Conclusions ST1A1 promotes intestinal inflammation and contributes to 5-ASA resistance by activating the EGFR-MAPK pathway, reducing 5-ASA uptake, and increasing its metabolism. Targeting ST1A1 may enhance therapeutic efficacy and enable biomarker-guided precision therapy in UC.Abstract IDDF2026-ABS-0182 Figure 1",
  "authors": [
    {
      "affiliations": [
        "Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing, China"
      ],
      "name": "Xinyi Xu"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing, China"
      ],
      "name": "Yan Dan"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing, China"
      ],
      "name": "Jiuyue Ma"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing, China"
      ],
      "name": "Minsi Zhou"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing, China"
      ],
      "name": "Chenyue Xu"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing, China"
      ],
      "name": "Peng Li"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing, China"
      ],
      "name": "Shutian Zhang"
    },
    {
      "affiliations": [
        "Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China"
      ],
      "name": "Dan Tian"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing, China"
      ],
      "name": "Haiyun Shi"
    }
  ],
  "title": "IDDF2026-ABS-0182 ST1A1 attenuates 5-aminosalicylic acid uptake and promotes its metabolism in intestinal epithelial cells through EGFR-MAPK signaling in ulcerative colitis",
  "uid": "8ec10615-fa18-5b78-be8d-a8094a7448cf"
}