{
  "abstract": "Background Gastric cancer (GC) is one of the most common malignancies worldwide and it is the third leading cause of cancer-related death in China. While Helicobacter pylori is a known GC pathogen, its abundance declines in tumours and the role of other bacteria in GC metastasis remains unclear.Objective We aim to investigate the mechanisms of other bacteria influencing GC progression and metastasis.Design Integrated intratumoural microbiome-metabolome analysis identified GC-associated microbes and metabolites. We then demonstrated the pro-metastatic role of Acinetobacter baumannii (A. baumannii, Ab) and its metabolite nicotinic acid (NA) using genetic, molecular and in vivo approaches.Results The abundance of A. baumannii was significantly increased in GC tissues, correlating with advanced tumour stage and intratumoural NA levels. Fluorescence in situ hybridisation confirmed its colonisation in GC tumours. In co-culture systems, A. baumannii increased NA levels, enhancing nicotinamide adenine dinucleotide (NAD) metabolism and increasing 1-Methylnicotinamide accumulation in tumour cells. Mutagenesis of the bacterial NA synthase gene pncA confirmed that A. baumannii excreted an NA-dependent pro-metastasis effect. Mechanically, A. baumannii promotes GC metastasis by reprogramming tumour cell glucose metabolism, reducing oxidative phosphorylation while enhancing glycolysis and activating the hypoxia-inducible factor-1 pathway in GC cells through metabolites both in vivo and in vitro.Conclusions This study elucidates the role of A. baumannii in enhancing NAD metabolism in GC cells through NA synthesis, consequently promoting GC metastasis. These findings establish a microbiota-metabolism axis as a mechanistic foundation for developing targeted therapeutic strategies against GC metastasis.",
  "authors": [
    {
      "affiliations": [
        "Department of Surgical Oncology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Yan Yang"
    },
    {
      "affiliations": [
        "Department of Surgical Oncology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Rui Yang"
    },
    {
      "affiliations": [
        "Department of Surgical Oncology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Department of Burn, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China"
      ],
      "name": "Yiran Chen"
    },
    {
      "affiliations": [
        "Department of Surgical Oncology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Chao He"
    },
    {
      "affiliations": [
        "Department of Surgical Oncology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Yingzi Zhang"
    },
    {
      "affiliations": [
        "Department of Surgical Oncology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Jing He"
    },
    {
      "affiliations": [
        "Department of Surgical Oncology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Jing Zhang"
    },
    {
      "affiliations": [
        "Department of Surgical Oncology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Haohao Wang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China"
      ],
      "name": "Jingdan Liang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China"
      ],
      "name": "Zixin Deng"
    },
    {
      "affiliations": [
        "Department of Surgical Oncology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Lisong Teng"
    }
  ],
  "title": "Acinetobacter baumannii promotes gastric cancer metastasis via NA-mediated NAD metabolism reprogramming and glycolytic activation",
  "uid": "37ac2259-c343-5217-a927-11daf64b8381"
}