Enhanced interactions among gut mycobiomes with the deterioration of glycemic control

Jia-Lin He; Ya-Wen Zhao; Jia-Lu Yang; Jing-Meng Ju; Bing-Qi Ye; Jing-Yi Huang; Zhi-Hao Huang; Wan-Ying Zhao; Wei-Feng Zeng; Min Xia; Yan Liu

doi:10.1016/j.medj.2024.03.023

Enhanced interactions among gut mycobiomes with the deterioration of glycemic control

Med. 2024 Apr 18:S2666-6340(24)00135-1. doi: 10.1016/j.medj.2024.03.023. Online ahead of print.

Authors

Affiliations

¹ Guangdong Provincial Key Laboratory of Food, Nutrition and Health, and Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
² Guangdong Provincial Key Laboratory of Food, Nutrition and Health, and Department of Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
³ Guangdong Provincial Key Laboratory of Food, Nutrition and Health, and Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China. Electronic address: xiamin@mail.sysu.edu.cn.
⁴ Guangdong Provincial Key Laboratory of Food, Nutrition and Health, and Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China. Electronic address: liuyan215@mail.sysu.edu.cn.

PMID: 38670112
DOI: 10.1016/j.medj.2024.03.023

Abstract

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.

Findings: 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.

Fundings: This study was supported by MOST and NSFC of China.

Keywords: Translation to patients; glycemic control; gut mycobiome; insulin sensitivity; interaction network.