{
  "abstract": "Background Endometriosis is a debilitating gynaecological disorder with an elusive pathogenesis. While gut microbiota dysbiosis has been implicated, the causal role of gut-peritoneum microbial translocation and the specific mechanisms driving disease progression remain elusive. Notably, the role of peritoneal neutrophils and neutrophil extracellular traps (NETs) in the development of endometriosis remains unknown.Objective This study aims to delineate the pathogenic pathway linking gut microbiota to peritoneal neutrophil activation and the development of endometriosis.Design We combined single-cell RNA sequencing of clinical peritoneal fluid immune cells with functional validation in heterologous and homologous mice models. We further adopted microbial source-tracking analysis of patient cohorts and interventional strategies, including faecal microbiota transplantation (FMT) and administration of green fluorescent protein (GFP)-tagged Pseudomonas aeruginosa.Results We identified a unique membrane metalloendopeptidase (MME) positive neutrophil subset (Neu_MME) that is expanded in endometriosis and primed for NETs formation (NETosis). These Neu_MME released NETs in response to bacterial lipopolysaccharides (LPS), which directly captured endometrial cells and enhanced their proliferation and migration, driving lesion development. Accordingly, inhibiting NETosis or degrading NETs significantly suppressed endometriosis in mice. Furthermore, FMT from patients with endometriosis to mice disrupted the intestinal barrier, promoting the translocation of gut microbiota, particularly Pseudomonas, into the peritoneal cavity and the lesions. This translocated Pseudomonas was identified as a key driver of LPS-induced NETosis and disease progression.Conclusion Our findings define a gut-peritoneum axis in endometriosis, where gut-derived Pseudomonas triggers NETosis in peritoneal Neu_MME to promote disease, suggesting that targeting this bacterium or NETosis represents a viable therapeutic strategy.",
  "authors": [
    {
      "affiliations": [
        "Department of Gynecology and Obstetrics, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China",
        "Department of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China"
      ],
      "name": "Xiangguang Wu"
    },
    {
      "affiliations": [
        "Department of Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China"
      ],
      "name": "Mingfu Wu"
    },
    {
      "affiliations": [
        "Department of Gynecology, Zhuhai People's Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai, Guangdong, China"
      ],
      "name": "Huawen Li"
    },
    {
      "affiliations": [
        "Department of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China",
        "Department of Gynecology and Obstetrics, Qingyuan People’s Hospital, Qingyuan, Guangdong, China"
      ],
      "name": "Yang Yang"
    },
    {
      "affiliations": [
        "Department of Gynecology and Obstetrics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China"
      ],
      "name": "Huimin Shen"
    },
    {
      "affiliations": [
        "Department of Gynecology and Obstetrics, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Siyuan Huang"
    },
    {
      "affiliations": [
        "Department of Gynecology and Obstetrics, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China",
        "Department of Gynecology and Obstetrics, Shenzhen People’s Hospital, Shenzhen, Guangdong, China"
      ],
      "name": "Yuha Pan"
    },
    {
      "affiliations": [
        "Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translation Research Center, Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China"
      ],
      "name": "Liwen Tao"
    },
    {
      "affiliations": [
        "Department of Gynecology and Obstetrics, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Shuangshuang Guo"
    },
    {
      "affiliations": [
        "Department of Gynecology and Obstetrics, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China",
        "Department of Gynecology and Obstetrics, Zhongshan City People’s Hospital, Zhongshan, Guangdong, China"
      ],
      "name": "Jinjiao Chen"
    },
    {
      "affiliations": [
        "Department of Gynecology and Obstetrics, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China",
        "Department of Gynecology and Obstetrics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China"
      ],
      "name": "Yu Wu"
    },
    {
      "affiliations": [
        "Department of Gynecology and Obstetrics, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Xiaoqing Zhong"
    },
    {
      "affiliations": [
        "Department of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China"
      ],
      "name": "Shuangdi Li"
    },
    {
      "affiliations": [
        "Centre for Assisted Reproduction, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China"
      ],
      "name": "Binya Liu"
    },
    {
      "affiliations": [
        "The Key Laboratory of Advanced Interdisciplinary Studies, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, The First Affiliated Hospital of Guangzhou Medical University, GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Wenliang Zhang"
    },
    {
      "affiliations": [
        "Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translation Research Center, Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China"
      ],
      "name": "Ruixin Zhu"
    },
    {
      "affiliations": [
        "Department of Gynecology and Obstetrics, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Liangsheng Fan"
    },
    {
      "affiliations": [
        "Department of Gynecology and Obstetrics, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China",
        "Department of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China"
      ],
      "name": "Wei Wang"
    }
  ],
  "title": "Intraperitoneal translocation of gut microbiota induces NETosis and promotes endometriosis",
  "uid": "030491af-ef68-5d8d-b6d8-5f438f7830fe"
}