{
  "abstract": "Background Exercise training is a potent strategy for the management of chronic metabolic disorders. Our previous studies suggested that the gut microbiome plays an important role in exercise-induced benefits. In our established exercise cohort of Chinese men with obesity and prediabetes, ITS2 sequencing identified Xylaria nigripes as an exercise-responsive gut fungal species that was significantly enriched after 12 weeks of high-intensity training. However, whether this fungus exerts a direct regulatory effect on host metabolism remains unknown.Methods 8-week-old male C57BL6/J mice were fed a 45% high-fat diet for 8 weeks and then treated with a 7-day antibiotic cocktail administration (ampicillin 1g/L, metronidazole 1g/L, neomycin 1g/L, vancomycin 0.5 g/L, and fluconazole 0.5 mg/mL). They were assigned to receive live X. nigripes (100 mg/Kg body weight, obtained from Zhejiang Zuoli Pharmaceutical Limited Corporation, China), heat-killed X. nigripes (HK), or PBS by oral gavage for 4 weeks (n=6-8 per group). Metabolic phenotyping was performed, including body composition, oxygen consumption, glucose homeostasis, and insulin sensitivity. Intestinal barrier integrity was evaluated by gut permeability assessment and histomorphology analysis. Circulating lipopolysaccharide (LPS) and inflammatory gene expression, including IL-6, IL-1β, and TNF-α, was examined in the gut and white adipose tissue (WAT).Results Four weeks of X. nigripes monocolonization markedly reduced fat mass accumulation, augmented oxygen consumption, improved glucose metabolism, and enhanced insulin sensitivity, compared with the HK and PBS groups. Notably, X. nigripes also ameliorated gut barrier dysfunction, as evidenced by reduced intestinal permeability, prolonged gut length, and improved intestinal morphology. Moreover, these metabolic improvements were accompanied by a significant reduction in circulating LPS levels and decreased proinflammatory gene expression in both intestine and WAT, indicating both local and systemic anti-inflammation effects.Conclusions Our findings identify X. nigripes as a causal fungal effector relevant to exercise-elicited metabolic benefits in terms of glucose homeostasis and insulin sensitivity in vivo, at least partially through restoration of a gut barrier-LPS axis and attenuation of metabolic inflammation. Our data further imply that, beyond gut bacteria, gut mycobiome also serves as a potential therapeutic target for obesity-related insulin resistance.",
  "authors": [
    {
      "affiliations": [
        "Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong",
        "Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong"
      ],
      "name": "Yao Wang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong",
        "Department of Medicine, The University of Hong Kong, Hong Kong"
      ],
      "name": "Jiaming Wu"
    },
    {
      "affiliations": [
        "State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong",
        "Department of Medicine, The University of Hong Kong, Hong Kong"
      ],
      "name": "Jianyu Yao"
    },
    {
      "affiliations": [
        "State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong",
        "Department of Medicine, The University of Hong Kong, Hong Kong"
      ],
      "name": "Aimin Xu"
    }
  ],
  "title": "IDDF2026-ABS-0123 Xylaria Nigripes is a gut fungus effector associated with exercise-improved host glucose metabolism and insulin sensitivity",
  "uid": "41443b6c-babe-5ee3-8b7f-eb5fd57eeaf2"
}