{
  "abstract": "Background Cholestatic liver disease (CLD) is a prevalent hepatic disorder with incompletely understood pathogenesis, and current therapeutic options remain limited. There is an urgent need for more effective preventive strategies. Notably, the contribution of the gut mycobiota to CLD pathogenesis remains unclear. This study aimed to characterize gut fungal dysbiosis in CLD and explore the molecular mechanism by which Aspergillus nidulans (A. nidulans) and its secondary metabolite sterigmatocystin (STE) drive CLD progression.Methods We performed internal transcribed spacer (ITS) sequencing in human CLD patients and mouse CLD models, conducted fungal depletion and A. nidulans colonization in mice, generated stcA-knockout A. nidulans via homologous recombination, and applied single-nucleus RNA-sequencing, hepatocyte organoids and cell lines for mechanistic validation.Results Gut fungal dysbiosis was confirmed in CLD patients and mice ( IDDF2026-ABS-0354 Figure 1); fungal depletion alleviated CLD in mice (IDDF2026-ABS-0354 Figure 2). A. nidulans was significantly enriched in CLD, and its colonization aggravated liver injury (IDDF2026-ABS-0354 Figure 3). STE was identified as the pathogenic metabolite (IDDF2026-ABS-0354 Figure 4). Knockout of stcA, a key gene for STE production in A. nidulans, reduced STE production and CLD severity (IDDF2026-ABS-0354 Figure 5). Mechanistically, STE directly interacted with the palmitoyltransferase Zdhhc7, triggering Fas palmitoylation in hepatocytes, thereby stabilizing the Fas protein and inducing hepatocyte apoptosis (IDDF2026-ABS-0354 Figure 6).Conclusions Gut mycobiota contributes to CLD pathogenesis via the A. nidulans-STE-Fas axis, potentially offering a novel therapeutic strategy to mitigate CLD severity.Abstract IDDF2026-ABS-0354 Figure 1Abstract IDDF2026-ABS-0354 Figure 2Abstract IDDF2026-ABS-0354 Figure 3Abstract IDDF2026-ABS-0354 Figure 4Abstract IDDF2026-ABS-0354 Figure 5Abstract IDDF2026-ABS-0354 Figure 6",
  "authors": [
    {
      "affiliations": [
        "Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, China"
      ],
      "name": "Yuanyuan Lei"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, China"
      ],
      "name": "Jinzhi Mo"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Army Medical University Daping Hospital, Chongqing, China"
      ],
      "name": "Tao Yuan"
    },
    {
      "affiliations": [
        "College of Pharmaceutical Sciences, Southwest University, Chongqing, China"
      ],
      "name": "Yi Zou"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, China"
      ],
      "name": "Bo Tang"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, The Second Affiliated Hospital of Army Medical University, Chongqing, China"
      ],
      "name": "Shiming Yang"
    }
  ],
  "title": "IDDF2026-ABS-0354 The gut fungus aspergillus nidulans promotes cholestatic liver injury through a secondary metabolite sterigmatocystin",
  "uid": "673a60e7-fa70-5f92-aec3-89723c7f3cec"
}