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

Area of Science:

• Microbiome research
• Metabolic health
• Dietary lipidomics

Background:

• Gut fungi (mycobiome) play a crucial role in host health.
• Diet significantly influences both the gut mycobiome and host metabolic status.
• Plasma n-3 polyunsaturated fatty acids (PUFAs) are key dietary lipids linked to metabolic health.

Purpose of the Study:

• To investigate the association between plasma n-3 PUFAs and the gut mycobiome.
• To explore the relationship between n-3 PUFA-associated gut fungi and type 2 diabetes (T2D) and glycemic phenotypes.
• To elucidate the potential mechanisms involving bile acids and fungal interactions.

Main Methods:

• Meta-analysis of four human cohorts to identify fungal genera associated with plasma total n-3 PUFA.
• Analysis of associations between specific fungal genera, fasting blood glucose, and glycated hemoglobin.
• Investigating the interaction between n-3 PUFA and Kodamaea on T2D in human and mouse models.
• Assessing the relationship between Kodamaea colonization and primary bile acid enrichment.

Main Results:

• Four fungal genera, including Debaryomyces, Kodamaea, and Wickerhamomyces, were inversely associated with plasma total n-3 PUFA.
• Wickerhamomyces showed a positive association with fasting blood glucose and glycated hemoglobin.
• An interaction between n-3 PUFA and Kodamaea influenced T2D risk, particularly in Kodamaea-free individuals.
• Kodamaea colonization was linked to an enrichment of specific primary bile acids.

Conclusions:

• Plasma n-3 PUFAs are associated with specific gut fungal genera, notably Kodamaea.
• These n-3 PUFA-associated fungi may modulate host glucose homeostasis and T2D risk.
• The findings highlight a potential mechanism involving bile acid metabolism in the gut mycobiome-host metabolic axis.