{
  "abstract": "Background Current microbiome-based therapeutics face two prominent issues: the limited clinical efficacy of probiotics and the significant variability in the efficacy of microbiota transplantation across different diseases. Although washed microbiota transplantation (WMT) is a new faecal microbiota transplantation, a single therapeutic agent cannot be universally effective for multiple dysbiosis-related diseases.Objective We introduced a new therapeutic concept, X-augmented WMT (X-auWMT), which combines a disease-specific beneficial microbe, ‘X’, with WMT to enhance its effectiveness. Our goal was to identify a candidate ‘X’ bacterium to augment WMT efficacy and examine the efficacy of X-auWMT in animal models of radiation enteritis (RE).Design We conducted a prospective, non-randomised cohort study on a cohort of abdominal or pelvic cancer patients who developed RE after radiotherapy to identify a potential beneficial microbe. We used RE mouse models to evaluate the efficacy of X-auWMT compared with WMT. Multiomics analyses and experiments were undertaken to elucidate the underlying mechanisms.Results WMT significantly alleviated multiple clinical symptoms in RE patients compared with routine treatments. We identified Holdemanella biformis as a candidate ‘X’ bacterium within the RE cohort and developed Hb-auWMT. Hb-auWMT significantly mitigated radiation-induced injury compared with WMT, exhibiting enhanced anti-apoptotic effects, improved maintenance of epithelial hypoxia, increased Treg cell levels and elevated butyrate and valerate levels in the RE mouse model. PPAR-γ is an essential pathway for the therapeutic efficacy of Hb-auWMT.Conclusions This study overcomes the aforementioned recognised limitations with probiotics and microbiota transplantation and provides a new research paradigm in the concept of microbiome-based therapeutics.",
  "authors": [
    {
      "affiliations": [
        "Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Weihong Wang"
    },
    {
      "affiliations": [
        "Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "You Yu"
    },
    {
      "affiliations": [
        "Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Rui Wang"
    },
    {
      "affiliations": [
        "Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Yaxue Wang"
    },
    {
      "affiliations": [
        "CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China"
      ],
      "name": "Xiao Ding"
    },
    {
      "affiliations": [
        "Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Gaochen Lu"
    },
    {
      "affiliations": [
        "Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Chen Lu"
    },
    {
      "affiliations": [
        "Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Chenchen Liang"
    },
    {
      "affiliations": [
        "Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Sheng Zhang"
    },
    {
      "affiliations": [
        "The Second Abdominal Surgery Department, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China"
      ],
      "name": "Bo Yi"
    },
    {
      "affiliations": [
        "Department of Biostatistics, Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Jianling Bai"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Lizhen Zhang"
    },
    {
      "affiliations": [
        "Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Pan Li"
    },
    {
      "affiliations": [
        "Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Quan Wen"
    },
    {
      "affiliations": [
        "Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Bota Cui"
    },
    {
      "affiliations": [
        "Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Faming Zhang"
    }
  ],
  "title": "Holdemanella biformis augments washed microbiota transplantation for the treatment of radiation enteritis",
  "uid": "1ec5d628-7ff7-5cd7-af67-ad8437fca9b6"
}