{
  "abstract": "Background Gastrointestinal acute graft-versus-host disease (GI-aGVHD) is one of the main complications of patients undergoing allogenic haematopoietic stem cell transplantation (allo-HSCT). A deeper understanding of the mechanisms of sustaining intestinal homeostasis is essential.Objective Here, we investigated micro-organisms and microbial metabolites that were crucial for intestinal homeostasis in the context of GI-aGVHD management.Design We profiled the gut microbiota, immune indices and gut metabolism of 71 patients undergoing allo-HSCT. Initially, we set up a mouse aGVHD model to confirm the effect of Bacteroides fragilis type VI secretion system (T6SS) on aGVHD progression. Subsequently, we applied 16S amplicon sequencing and metabolic profiling to reveal the function of B. fragilis T6SS on microbial structure intestinal and metabolome. Finally, the mediation package was used to validate our findings in clinical samples.Results A higher abundance of Bacteroides spp contributes to reducing the incidence of GI-aGVHD, and the T6SS is required for Bacteroides spp protection on aGVHD. T6SS-mediated antagonism regulates the structure and composition of gut microbiota, affecting the entire gut metabolome, particularly the bile acids metabolism, subsequently reducing inflammation response in the intestine and protecting intestinal barrier integrity. Notably, accumulating primary bile acids such as chenodeoxycholic acid exacerbated aGVHD by enhancing the activation of T cells. Mediation analysis further validated that T6SS affects the incidence of GI-aGVHD through its effect on primary bile acid metabolism.Conclusions T6SS in commensal bacteria could modulate bile acid metabolism, potentially impacting aGVHD outcomes and offering a novel target for therapeutic interventions.",
  "authors": [
    {
      "affiliations": [
        "National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China",
        "Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, China"
      ],
      "name": "Pengfei Li"
    },
    {
      "affiliations": [
        "National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China",
        "Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, China"
      ],
      "name": "Qiyi Lei"
    },
    {
      "affiliations": [
        "National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China",
        "Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, China"
      ],
      "name": "Xinghao Yu"
    },
    {
      "affiliations": [
        "National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China",
        "Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, China"
      ],
      "name": "Ying Shen"
    },
    {
      "affiliations": [
        "National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China",
        "Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, China"
      ],
      "name": "Yiyin Chen"
    },
    {
      "affiliations": [
        "National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China",
        "Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, China"
      ],
      "name": "Chang Hou"
    },
    {
      "affiliations": [
        "National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China",
        "Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, China"
      ],
      "name": "Bo Hu"
    },
    {
      "affiliations": [
        "National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China",
        "Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, China"
      ],
      "name": "Yanfang Cui"
    },
    {
      "affiliations": [
        "National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China",
        "Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, China"
      ],
      "name": "Zhihua Liu"
    },
    {
      "affiliations": [
        "Department of Pharmacy, Clinical Pharmacology Research Lab, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China"
      ],
      "name": "Yi Qin"
    },
    {
      "affiliations": [
        "Immunology Translational Research Programme, Department of Microbiology of Immunology, Yong Loo Lin School of Medicine, Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore"
      ],
      "name": "Haiyan Liu"
    },
    {
      "affiliations": [
        "National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China",
        "Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, China"
      ],
      "name": "Dandan Lin"
    },
    {
      "affiliations": [
        "National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China",
        "Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, China"
      ],
      "name": "Yang Xu"
    },
    {
      "affiliations": [
        "National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China",
        "Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, China"
      ],
      "name": "Depei Wu"
    }
  ],
  "title": "Commensal Bacteroides T6SS alleviate GI-aGVHD via mediating gut microbiota composition and bile acids metabolism",
  "uid": "da18ab0a-d7e8-5e42-a98f-4cb03c53a8f1"
}