IDDF2023-ABS-0028 Integrative multi-omics reveal associations between gut mycobiome and metabolic benefits of physical exercise in obese individuals with prediabetes

Background

Gut microbes play an essential role in orchestrating holistic metabolic health. Our previous findings demonstrated that gut bacteria was shaped by exercise in humans and determined excise responsiveness in terms of glucose and insulin control. However, the impact of intestinal fungi on exercise remains unclear, especially when compared to the bacterial microbiome. In this study, we aimed first to investigate the changes in the gut mycobiome during exercise. Then, we plan to determine further the potential association of intestinal fungi in mediating exercise-elicited metabolic outcomes.

Methods

We conducted a randomized controlled trial (RCT) of a 12-week exercise intervention in overweight Chinese males with prediabetes (n=40). Clinical parameters and biological samples including stool and blood were collected before and after the training. Fecal fungal composition and bacterial profiles were analyzed using internal transcribed spacer 2 (ITS2) sequencing and shotgun metagenomic data, respectively. Circulating metabolite concentrations were assayed using targeted metabolomics, while blood cytokines and hormones were measured by Olink proteomics.

Results

Exercise training significantly increased fungal ecological diversity and connectivity and shifted the gut mycobiome structure. Changes in fungal abundance were linked to exercise-induced metabolic phenotypes, bacterial microbiome, and circulating metabolomics and proteomics profiles. Of note, differential alternations in fungal compositions were found between exercise responders and non-responders. Interestingly, applying baseline fungal signatures predicting exercise responsiveness in terms of insulin sensitivity with an area under the receiver operating characteristic (AUROC) of 0.907 AUROC: 0.907 (95% CI: 0.840 to 0.974), which was further validated in our independent cohort (n=31) with AUROC: 0.745 (95% CI: 0.695 to 0.795).

Conclusions

Our muti-omics analysis reveals that changes in the gut mycobiome are closely associated with the metabolic benefits of exercise training, indicating the importance of gut fungi in regulating host metabolism. Moreover, we identified that the differential changes of gut mycobiome were linked with exercise responsiveness regarding diabetes prevention, which highlights the potential of targeting enteric fungi signatures as a novel approach for developing precision-based exercise protocols in clinical implementation.