背景:肠道真菌与健康和疾病密切相关;然而,其在2型糖尿病(T2DM)进展中的作用尚不清楚.这里,我们采用了一项多组学方法来探讨肠道真菌在血糖控制恶化中的作用.
方法:350名没有低血糖治疗的参与者被邀请进行标准的口服葡萄糖耐量试验,以确定他们的血糖控制状况。通过内部转录间隔区测序鉴定了肠道真菌群,通过基因分型阵列确定宿主遗传学,血浆代谢产物用非靶向液相色谱-质谱法测定。
结果:真菌的丰富度较高,而其差异性明显较低,在T2DM参与者中。此外,真菌的多样性和组成与胰岛素敏感性和胰岛β细胞功能密切相关。随着血糖控制的加剧,真菌类群之间的共现网络变得越来越复杂,相互作用网络的复杂性与胰岛素敏感性呈负相关.孟德尔随机化分析进一步证明了古细菌类,镰刀菌属,和Neoascochyta属与葡萄糖代谢受损有因果关系。此外,与代谢组学的综合分析表明,增加4-羟基-2-氧戊二酸,酮亮氨酸,溶血磷脂酰胆碱(20:3/0:0),和N-乳酰-苯丙氨酸,但溶血磷脂酰胆碱(O-18:2)减少,作为关键分子连接镰刀菌属对胰岛素敏感性的不利影响。
结论:我们的研究揭示了肠道真菌紊乱与T2DM进展之间的强烈关联,并强调了靶向肠道真菌群治疗T2DM的潜力。
结果:本研究得到了国家自然科学基金和国家自然科学基金的支持。
BACKGROUND: The gut mycobiome is closely linked to health and disease; however, its role in the progression of type 2 diabetes mellitus (T2DM) remains obscure. Here, a multi-omics approach was employed to explore the role of intestinal fungi in the deterioration of glycemic control.
METHODS: 350 participants without hypoglycemic therapies were invited for a standard oral glucose tolerance test to determine their status of glycemic control. The gut mycobiome was identified through internal transcribed spacer sequencing, host genetics were determined by genotyping array, and plasma metabolites were measured with untargeted liquid chromatography mass spectrometry.
RESULTS: The richness of fungi was higher, whereas its dissimilarity was markedly lower, in participants with T2DM. Moreover, the diversity and composition of fungi were closely associated with insulin sensitivity and pancreatic β-cell functions. With the exacerbation of glycemic control, the co-occurrence network among fungus taxa became increasingly complex, and the complexity of the interaction network was inversely associated with insulin sensitivity. Mendelian randomization analysis further demonstrated that the Archaeorhizomycetes class, Fusarium genus, and Neoascochyta genus were causally linked to impaired glucose metabolism. Furthermore, integrative analysis with metabolomics showed that increased 4-hydroxy-2-oxoglutaric acid, ketoleucine, lysophosphatidylcholine (20:3/0:0), and N-lactoyl-phenylalanine, but decreased lysophosphatidylcholine (O-18:2), functioned as key molecules linking the adverse effect of Fusarium genus on insulin sensitivity.
CONCLUSIONS: Our study uncovers a strong association between disturbance in gut fungi and the progression of T2DM and highlights the potential of targeting the gut mycobiome for the management of T2DM.
RESULTS: This study was supported by MOST and NSFC of China.