Serum Metabolomics Reveals Potential Differences in Gut Microbiota-Associated Metabolites in Twins Discordant for Type 1 Diabetes

We investigated serum metabolites in monozygotic (MZ) and dizygotic (DZ) twins discordant for type 1 diabetes (T1D) to explore potential environmental factors with a focus on differences in gut microbiota-associated metabolites 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 exhibited significant differences between T1D and non-T1D individuals. 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. These findings suggest metabolite dysregulation associated with gut dysbiosis was observed. However, further validation of our findings in a larger cohort is needed.