{
  "abstract": "Background Certain gut bacteria are associated with improved responses to immunotherapy.Objective We aim to identify bacteria that inhibit colorectal cancer (CRC) progression and enhance immunotherapy efficacy.Design The abundance of bacteria in CRC patients was evaluated in our in-house cohorts and validated in published datasets. The effect of candidate bacterium with anti-PD-1 therapy was determined in two syngeneic mouse models of MC38 (microsatellite instability-high) and CT26 (microsatellite stable, MSS), transgenic Apcmin/+ mice and azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC tumourigenesis model. Immune landscape changes were identified by multicolour flow cytometry and immunohistochemistry staining. Metabolomic profiling was performed on stool, serum and tumour tissues.Results Bifidobacterium catenulatum was significantly depleted in stool samples of 110 CRC patients compared with 112 healthy controls, which was further validated in 3 published metagenomic datasets comprising 198 CRC patients and 176 normal subjects. Oral administration of B. catenulatum inhibited tumour growths in multiple CRC models including MC38 and CT26 syngeneic models, Apcmin/+ mice and AOM/DSS-induced CRC. Notably, B. catenulatum synergised with anti-PD-1 therapy through enhancing intratumoural CD8+ T cell infiltration in MSS CRC models of Apcmin/+ mice and CT26 allografts. B. catenulatum-derived acetate was identified as the functional metabolite. Mechanistically, acetate directly bound to MCT-4 in CD8+ T cells and activated mitogen-activated protein kinase signalling. Pharmacological and genetic MCT4 ablation abolished acetate-mediated CD8+ T cell activation in vitro.Conclusion B. catenulatum suppresses colorectal tumourigenesis through generating acetate, which also improves anti-PD-1 efficacy through activating CD8+ T cells in MSS CRC. B. catenulatum is a potential adjuvant to improve immunotherapy against CRC.",
  "authors": [
    {
      "affiliations": [
        "Department of High Talent, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China",
        "Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China"
      ],
      "name": "Xiang Li"
    },
    {
      "affiliations": [
        "Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China"
      ],
      "name": "Mingxu Xie"
    },
    {
      "affiliations": [
        "Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore"
      ],
      "name": "Jason Xing Kang"
    },
    {
      "affiliations": [
        "Department of High Talent, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China"
      ],
      "name": "Yue Chen"
    },
    {
      "affiliations": [
        "Department of High Talent, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China"
      ],
      "name": "Jing Han"
    },
    {
      "affiliations": [
        "Department of High Talent, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China"
      ],
      "name": "Yinnan Chen"
    },
    {
      "affiliations": [
        "Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China"
      ],
      "name": "Qian Chen"
    },
    {
      "affiliations": [
        "Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China"
      ],
      "name": "Tianyu Yu"
    },
    {
      "affiliations": [
        "Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China"
      ],
      "name": "Shuyan Liu"
    },
    {
      "affiliations": [
        "Department of High Talent, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China"
      ],
      "name": "Zhenlin Ouyang"
    },
    {
      "affiliations": [
        "The First Affiliated Hospital of Xi’an Jiaotong University, Yulin Hospital, Yulin, Shaanxi, China"
      ],
      "name": "Qiong Sun"
    },
    {
      "affiliations": [
        "Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China"
      ],
      "name": "Kai Li"
    },
    {
      "affiliations": [
        "Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China"
      ],
      "name": "Shaoqiang Zhang"
    },
    {
      "affiliations": [
        "Department of High Talent, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China",
        "The First Affiliated Hospital of Xi’an Jiaotong University, Yulin Hospital, Yulin, Shaanxi, China",
        "Department of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People's Republic of China"
      ],
      "name": "Junjun She"
    },
    {
      "affiliations": [
        "Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China",
        "The First Affiliated Hospital of Xi’an Jiaotong University, Yulin Hospital, Yulin, Shaanxi, China"
      ],
      "name": "Jun Yu"
    }
  ],
  "title": "Bifidobacterium catenulatum boosts anti-PD-1 efficacy in microsatellite stable colorectal cancer via activating CD8+ T cells",
  "uid": "6367e3c7-0fc2-540f-95c4-db7c1717c07e"
}