Exploring Microbiota-Associated Metabolites in Twins Discordant for Type 1 Diabetes

Identify microbial and microbiota-associated metabolites in monozygotic (MZ) and dizygotic (DZ) twins discordant for type 1 diabetes (T1D) to gain insight into potential environmental factors that may influence T1D.

Serum samples from 39 twins discordant for T1D were analyzed using a semi-targeted metabolomics approach via liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS). Statistical analyses identified significant metabolites (p < 0.1) within three groups: All twins (combined group), MZ twins, and DZ twins.

Thirteen metabolites were identified as significant. 3-indoxyl sulfate and 5-hydroxyindole were significantly reduced in T1D individuals across all groups. Carnitine was reduced, and threonine, muramic acid, and 2-oxobutyric acid were significantly elevated in both All and MZ groups. Allantoin was significantly reduced and 3-methylhistidine was significantly elevated in All and DZ groups.

Metabolite dysregulation associated with gut dysbiosis was observed. However, further validation of our findings in a larger cohort is needed.

Why did we undertake this study? We believed this cohort of twins discordant for type 1 diabetes (T1D) would allow for control over genetic variability to examine environmental factors.What is the specific question(s) we wanted to answer? We aimed to identify differences in microbial and microbiota-associated metabolites in twins discordant for T1D to examine the effect of the gut microbiome on T1D.What did we find? Thirteen metabolites were identified as significantly different.What are the implications of our findings? Our results show the dysregulation of several microbial metabolites in twin pairs, suggesting that the gut microbiome plays a role in the pathogenesis of T1D.