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<p>The pivotal role of gut fungi (i.e., mycobiome) in host health is increasingly recognized. Diet is a critical determinant factor for both gut fungi and host metabolic health. This study aimed to investigate the associations of plasma n-3 polyunsaturated fatty acids (PUFAs), an important dietary lipid component, with gut mycobiome and explore the relationship of n-3 PUFA-related gut fungi with type 2 diabetes (T2D) and glycemic phenotypes. Here, we identified four fungal genera that were inversely associated with plasma total n-3 PUFA in the discovery cohort. Among these, <i>Debaryomyces</i>, <i>Kodamaea</i>, and <i>Wickerhamomyces</i> were consistently associated with total n-3 PUFA in the metaanalysis of 4 human cohorts (FDR-meta&lt;0.1). We also found that <i>Wickerhamomyces</i> was positively associated with host fasting blood glucose and glycated hemoglobin (FDR&lt;0.05). Moreover, we observed an interaction between n-3 PUFA and <i>Kodamaea</i> on T2D (<i>P</i>-interaction=0.02), which was confirmed in the mice study. In human and mice studies, the inverse associations between n-3 PUFA and glycemic phenotypes were only observed in the <i>Kodamaea</i>-free population. Additionally, the enrichment of specific primary bile acids, namely cholic acid and its conjugated forms, was associated with <i>Kodamaea</i> colonization. Our results indicate that n-3 PUFA is associated with specific gut fungal genera, which may, in turn, affect host glucose homeostasis.</p>

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Association of plasma n-3 polyunsaturated fatty acid with gut mycobiome and implications for glucose homeostasis

  • 期刊论文

  • 发表日期：

    2025年6月12日

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  • Congmei Xiao,
  • Yue Xi,
  • Xinyu Wang,
  • Chang Gao,
  • Ruiqi Shi,
  • Zelei Miao,
  • Yuhui Liang,
  • Wanglong Gou,
  • Ke Zhang,
  • Chun Wang,
  • Xinxiu Liang,
  • Meng Ye,
  • Jun Tang,
  • Menglei Shuai,
  • Bingbing Li,
  • Yuanqing Fu,
  • Yan Yan,
  • Haili Zhong,
  • Zengliang Jiang,
  • Yu-ming Chen,
  • Ju-Sheng Zheng

摘要

The pivotal role of gut fungi (i.e., mycobiome) in host health is increasingly recognized. Diet is a critical determinant factor for both gut fungi and host metabolic health. This study aimed to investigate the associations of plasma n-3 polyunsaturated fatty acids (PUFAs), an important dietary lipid component, with gut mycobiome and explore the relationship of n-3 PUFA-related gut fungi with type 2 diabetes (T2D) and glycemic phenotypes. Here, we identified four fungal genera that were inversely associated with plasma total n-3 PUFA in the discovery cohort. Among these, Debaryomyces, Kodamaea, and Wickerhamomyces were consistently associated with total n-3 PUFA in the metaanalysis of 4 human cohorts (FDR-meta<0.1). We also found that Wickerhamomyces was positively associated with host fasting blood glucose and glycated hemoglobin (FDR<0.05). Moreover, we observed an interaction between n-3 PUFA and Kodamaea on T2D (P-interaction=0.02), which was confirmed in the mice study. In human and mice studies, the inverse associations between n-3 PUFA and glycemic phenotypes were only observed in the Kodamaea-free population. Additionally, the enrichment of specific primary bile acids, namely cholic acid and its conjugated forms, was associated with Kodamaea colonization. Our results indicate that n-3 PUFA is associated with specific gut fungal genera, which may, in turn, affect host glucose homeostasis.