Xiao Congmei, Xi Yue, Wang Xinyu, Gao Chang, Shi Ruiqi, Miao Zelei, Liang Yuhui, Gou Wanglong, Zhang Ke, Wang Chun, Liang Xinxiu, Ye Meng, Tang Jun, Shuai Menglei, Li Bingbing, Fu Yuanqing, Yan Yan, Zhong Haili, Jiang Zengliang, Chen Yu-Ming, Zheng Ju-Sheng
Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, 310030, China.
Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510275, China.
Sci China Life Sci. 2025 Jun 12. doi: 10.1007/s11427-024-2850-y.
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.
肠道真菌（即真菌群落）在宿主健康中的关键作用日益受到认可。饮食是肠道真菌和宿主代谢健康的关键决定因素。本研究旨在调查血浆n-3多不饱和脂肪酸（PUFAs）（一种重要的膳食脂质成分）与肠道真菌群落的关联，并探索与n-3多不饱和脂肪酸相关的肠道真菌与2型糖尿病（T2D）和血糖表型之间的关系。在此，我们在发现队列中鉴定出四个与血浆总n-3多不饱和脂肪酸呈负相关的真菌属。其中，德巴利酵母属、科达酵母属和威克汉姆酵母属在4个人类队列的荟萃分析中始终与总n-3多不饱和脂肪酸相关（FDR-荟萃分析<0.1）。我们还发现威克汉姆酵母属与宿主空腹血糖和糖化血红蛋白呈正相关（FDR<0.05）。此外，我们观察到n-3多不饱和脂肪酸与科达酵母属在2型糖尿病方面存在相互作用（P-相互作用=0.02），这在小鼠研究中得到了证实。在人类和小鼠研究中，仅在无科达酵母属的人群中观察到n-3多不饱和脂肪酸与血糖表型之间的负相关。此外，特定初级胆汁酸（即胆酸及其共轭形式）的富集与科达酵母属的定殖有关。我们的结果表明，n-3多不饱和脂肪酸与特定的肠道真菌属相关，这反过来可能会影响宿主的葡萄糖稳态。
