{
  "abstract": "Background Gut microbiota has been widely recognised as playing a critical role in maintaining immune imbalance and the development of rheumatoid arthritis (RA). As key roles mediating interkingdom crosstalk among plants, microbiomes and mammals, plant-derived exosome-like nanoparticles (ELNs) could use lipids and microRNA components to precisely modulate gene expression of gut microbiota, showing potential as a dietary intervention for RA treatment.Objective We aimed to investigate gut microbiota–immune interactions inducing immune dysregulation in RA and explore potential applications of edible plant-derived ELNs for RA treatment through gut microbiota manipulation.Design Combinations of microbial analysis of clinical cohort, metabolomics, in vivo and in vitro examination were performed to establish potential gut-immune mechanisms for interventions. Several representative edible plants ELNs were chosen to compare the modulation effects based on the above mechanism. Small RNA sequencing and lipidomic analysis were performed to identify key components and reveal the related mechanisms mediating therapeutic effects.Results Ruminococcus gnavus was significantly enriched in RA and aggravated arthritis through secreting phenylethylamine (PEA) to induce excessive neutrophil extracellular traps (NETs) formation. Among several plants ELNs, Pueraria lobata-derived ELNs (Pu-ELNs) were preferentially taken up by R. gnavus and decreased PEA production. Mechanistically, the lipid components of Pu-ELNs induced intestinal accumulation of ELN-derived gma-miR4412, which reduces phenylalanine decarboxylase (PDC) expression, relieving the arthritis aggravation caused by R. gnavus through acting on the PEA-Bruton’s tyrosine kinase (BTK)-NETs axis.Conclusions Our findings suggest the crucial role of R. gnavus in aggravating RA and underscore the application of plant-derived ELNs for microbiota manipulation.",
  "authors": [
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, China",
        "Department of Traditional Chinese Internal Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China"
      ],
      "name": "Bingqi Han"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-Sen University, Guangzhou, China"
      ],
      "name": "Yutong Jiang"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China"
      ],
      "name": "Haihua Liu"
    },
    {
      "affiliations": [
        "Department of Anesthesiology, Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China"
      ],
      "name": "Fangling Zhang"
    },
    {
      "affiliations": [
        "Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Yi Xu"
    },
    {
      "affiliations": [
        "Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Zhuang Li"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, China"
      ],
      "name": "Songyuan Zheng"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, China",
        "Department of Traditional Chinese Internal Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China"
      ],
      "name": "Fopei Ma"
    },
    {
      "affiliations": [
        "Department of Traditional Chinese Medicine, People’s Hospital of Yangjiang, Yangjiang, China"
      ],
      "name": "Hao Shi"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-Sen University, Guangzhou, China"
      ],
      "name": "Xinlei Jia"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, China"
      ],
      "name": "Jinhao Chen"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, China"
      ],
      "name": "Leyi Tan"
    },
    {
      "affiliations": [
        "Department of Traditional Chinese Medicine, People’s Hospital of Yangjiang, Yangjiang, China"
      ],
      "name": "Huijie Fan"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynecology, The First Affiliated Hospital, Ningbo University, Ningbo, China",
        "Ningbo Key Laboratory of Human Microbiology and Precision Medicine, The First Affiliated Hospital, Ningbo University, Ningbo, China"
      ],
      "name": "Shuaijun Lv"
    },
    {
      "affiliations": [
        "Southern Medical University, Guangzhou, China"
      ],
      "name": "Lei Gao"
    },
    {
      "affiliations": [
        "School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China"
      ],
      "name": "Xiaoshan Zhao"
    },
    {
      "affiliations": [
        "Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China",
        "Shenzhen Key Laboratory of Gastrointestinal Microbiota and Disease, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Hong-Wei Zhou"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, China"
      ],
      "name": "Juan Li"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, China"
      ],
      "name": "Mukeng Hong"
    }
  ],
  "title": "Pueraria lobata-derived exosome-like nanovesicles alleviate rheumatoid arthritis via targeting Ruminococcus gnavus phenylethylamine production",
  "uid": "4cba0a49-5cb3-5ecd-b09a-ab4016d54325"
}