{
  "abstract": "Background Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease characterized by impaired colonic mucosal barrier. Studies have shown that the pathogenesis of UC is closely associated with gut microbiota dysbiosis. Dynamin-related protein 1 (Drp1), a key regulator of mitochondrial fission, has recently been found to play an important role in maintaining intestinal homeostasis and regulating inflammatory responses. However, whether Drp1 participates in the pathogenesis of UC by modulating the gut microbiota remains unclear. Therefore, this study aims to investigate whether myeloid-specific Drp1 is involved in the progression of UC by regulating gut microbiota structure.Methods Myeloid-specific Drp1 knockout mice (Drp1 fl/fl Lyz2cre) were generated using CRISPR/Cas9 technology, followed by induction of UC via administration of 3% DSS for 7 days. Intestinal barrier function, inflammatory levels, and gut microbiota composition were systematically evaluated through dynamic monitoring of body weight, stool consistency, and disease activity index (DAI), along with colon length measurement, hematoxylin and eosin (H&E) staining, Alcian blue-periodic acid-Schiff (AB-PAS) staining, and 16S rRNA sequencing.Results In this study, a colitis model was established using Drp1 fl/fl Lyz2cre mice, and we found that myeloid-specific Drp1 deficiency alleviated DSS-induced intestinal damage. Compared with the control group, the knockout mice exhibited significantly reduced body weight loss (IDDF2026-ABS-0405 Figure 1(A) Protective effects of myeloid-specific Drp1-deficiency against DSS-induced colitis), markedly decreased disease activity index (DAI) scores (IDDF2026-ABS-0405 Figure 1(B) Protective effects of myeloid-specific Drp1-deficiency against DSS-induced colitis), and histopathological damage (IDDF2026-ABS-0405 Figure 1(C,D,E) Protective effects of myeloid-specific Drp1-deficiency against DSS-induced colitis) and significant improvements in colon shortening (IDDF2026-ABS-0405 Figure 1(F,G) Protective effects of myeloid-specific Drp1-deficiency against DSS-induced colitis).16S rRNA sequencing results showed that OTU overlap Venn diagram, PLS-DA, and NMDS analysis (IDDF2026-ABS-0405 Figure 2(A,C,D) Myeloid-specific Drp1-deficiency modulates gut microbiota composition in DSS-induced colitis) revealed that myeloid-specific Drp1 deficiency altered the diversity of the gut microbiota in colitic mice and modulated bacterial abundance. Meanwhile, the stacked bar chart at the genus level and LEfSe analysis (IDDF2026-ABS-0405 Figure 2(B,E) Myeloid-specific Drp1-deficiency modulates gut microbiota composition in DSS-induced colitis) revealed an increase in the abundance of the beneficial genus Akkermansia and a decrease in the abundance of the pathogenic genus Escherichia-Shigella.Conclusions Myeloid-specific Drp1 deficiency ameliorates DSS-induced murine ulcerative colitis by remodeling gut microbiota structure, promoting the enrichment of beneficial bacteria and reducing the abundance of pathogenic bacteria. Modulation of the gut microbiota by myeloid-specific Drp1 deficiency may provide a novel therapeutic strategy for the clinical management of ulcerative colitis.Abstract IDDF2026-ABS-0405 Figure 1Abstract IDDF2026-ABS-0405 Figure 2",
  "authors": [
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, School of Medicine, the Second Affiliated Hospital of South China University of Technology (Guangzhou First People’s Hospital), Guangzhou, Guangdong, China"
      ],
      "name": "Yitong Liao"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, School of Medicine, the Second Affiliated Hospital of South China University of Technology (Guangzhou First People’s Hospital), Guangzhou, Guangdong, China"
      ],
      "name": "Youlian Zhou"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, School of Medicine, the Second Affiliated Hospital of South China University of Technology (Guangzhou First People’s Hospital), Guangzhou, Guangdong, China"
      ],
      "name": "Chen Huang"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, School of Medicine, the Second Affiliated Hospital of South China University of Technology (Guangzhou First People’s Hospital), Guangzhou, Guangdong, China"
      ],
      "name": "Yan Zhang"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, School of Medicine, the Second Affiliated Hospital of South China University of Technology (Guangzhou First People’s Hospital), Guangzhou, Guangdong, China"
      ],
      "name": "Xue Guo"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, School of Medicine, the Second Affiliated Hospital of South China University of Technology (Guangzhou First People’s Hospital), Guangzhou, Guangdong, China"
      ],
      "name": "Jianhong Li"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, School of Medicine, the Second Affiliated Hospital of South China University of Technology (Guangzhou First People’s Hospital), Guangzhou, Guangdong, China"
      ],
      "name": "Jing Xu"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, School of Medicine, the Second Affiliated Hospital of South China University of Technology (Guangzhou First People’s Hospital), Guangzhou, Guangdong, China"
      ],
      "name": "Yongjian Zhou"
    }
  ],
  "title": "IDDF2026-ABS-0405 Myeloid-specific Drp1 deficiency alleviates murine ulcerative colitis by modulating gut microbiota structure",
  "uid": "cedfa4a5-9ceb-5775-8c42-905a7ab2212f"
}