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<p>The involvement of gut microbiota in metabolic disorders, including gallstones, has been increasingly reported, mainly focusing on the study of gut bacteria. However, as a relatively small proportion of intestinal microorganisms, the homeostasis of fungi still plays an important role in maintaining the health of the body. Our study showed that compared with healthy volunteers, patients with gallstones showed intestinal fungal dysregulation, which was marked by increased fungal biodiversity and changes in composition. At the same time, patients with gallstones also showed changes in fungal-bacterial interactions. In order to determine the role of intestinal fungal dysbiosis in gallstone formation, we administered fluconazole (a broad-spectrum antifungal drug) to C57 mice on a lithogenic diet and found that the formation of gallstones in mice treated with fluconazole was reduced. We then gavaged mice with <i>Rhodotorula mucilaginosa</i> and discovered that it can promote gallstone formation. Further analysis, including liver metabolism determination, liver immunohistochemistry and immunofluorescence, revealed that intestinal fungi promoted liver neutrophil infiltration and neutrophil extracellular trap formation to aggravate gallstone formation. In addition, through liver transcriptome sequencing, we found that the effect of fluconazole on intestinal fungi may hinder the formation of gallstones by regulating multiple targets related to gallstones. In summary, our study determined the role of intestinal fungal disorders in promoting gallstone formation, and fluconazole can effectively inhibit gallstone formation.</p>

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Gut fungi exacerbates gallstone formation by activating neutrophil extracellular traps in the liver

  • 期刊论文

  • 发表日期：

    2026年1月7日

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  • Dongxu Lu,
  • Haoran Ding,
  • Shuo Feng,
  • Fenghe Hang,
  • Kaiwen Tian,
  • Zhenghao Huang,
  • Yucong Shi,
  • Dongbo Xue,
  • Liwei Liu,
  • Xianzhi Meng

摘要

The involvement of gut microbiota in metabolic disorders, including gallstones, has been increasingly reported, mainly focusing on the study of gut bacteria. However, as a relatively small proportion of intestinal microorganisms, the homeostasis of fungi still plays an important role in maintaining the health of the body. Our study showed that compared with healthy volunteers, patients with gallstones showed intestinal fungal dysregulation, which was marked by increased fungal biodiversity and changes in composition. At the same time, patients with gallstones also showed changes in fungal-bacterial interactions. In order to determine the role of intestinal fungal dysbiosis in gallstone formation, we administered fluconazole (a broad-spectrum antifungal drug) to C57 mice on a lithogenic diet and found that the formation of gallstones in mice treated with fluconazole was reduced. We then gavaged mice with Rhodotorula mucilaginosa and discovered that it can promote gallstone formation. Further analysis, including liver metabolism determination, liver immunohistochemistry and immunofluorescence, revealed that intestinal fungi promoted liver neutrophil infiltration and neutrophil extracellular trap formation to aggravate gallstone formation. In addition, through liver transcriptome sequencing, we found that the effect of fluconazole on intestinal fungi may hinder the formation of gallstones by regulating multiple targets related to gallstones. In summary, our study determined the role of intestinal fungal disorders in promoting gallstone formation, and fluconazole can effectively inhibit gallstone formation.