Identification of gut microbiome signatures and metabolites associated with albuminuria in type 2 diabetes

Abstract

Context: Type 2 diabetes is a growing global concern with serious complications, including kidney damage and cardiovascular morbidity and mortality. Monitoring albuminuria, which is associated with these complications, is crucial in optimal diabetes management. Gut microbiota composition has been suggested to impact albuminuria, but large studies with granular data are lacking.

Methods: We investigated the relationship between 1002 gut microbial species, 1308 plasma metabolites and albuminuria in 752 participants with type 2 diabetes from the Swedish CArdioPulmonary BioImage Study. To determine the relative abundance of species, we employed deep shotgun metagenomic sequencing of fecal samples. Plasma metabolites were analyzed using mass spectrometry-based methods.

Results: We identified three species that were associated with albuminuria, including Sellimonas intestinalis, Eggerthellales sp., Ellagibacter isourolithinifaciens. Two of these species were replicated in an independent pre-diabetic population (n=3,423) in SCAPIS. In total, 36 annotated metabolites were associated with the three albuminuria-signature species. Functional mapping of the signature species suggests a role in the regulation of the metabolites of imidazole propionate and trigonelline, which have previously been reported to play roles in the progression of albuminuria.

Conclusions: These findings provide additional evidence of the potential impact of microbial species and contribute to our understanding of the complex relationship between the gut microbiome, plasma metabolites, and albuminuria in individuals with diabetes.

Keywords: albuminuria; diabetic nephropathy; dysbiosis; gut microbiome; microbial signatures; type 2 diabetes.