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. Statistical analyses identified significant metabolites (P < 0.1) within three groups: all twins (combined group [All]), MZ twins, and DZ twins. Thirteen metabolites exhibited significant differences between individuals with T1D and those without T1D. Across all groups, 3-indoxyl sulfate and 5-hydroxyindole were significantly reduced in individuals with T1D. 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.
- We believed this cohort of twins discordant for type 1 diabetes (T1D) would allow for control over genetic variability to examine environmental factors.
- 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.
- Thirteen metabolites were identified as significantly different.
- Our results show dysregulation of several microbial metabolites in twin pairs, suggesting the role of the gut microbiome in T1D pathogenesis.

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