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

ObjectiveIdentify 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. Research Design and MethodsSerum 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. ResultsThirteen 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. ConclusionsMetabolite dysregulation associated with gut dysbiosis was observed. However, further validation of our findings in a larger cohort is needed. Article HighlightsO_LIWhy 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. C_LIO_LIWhat 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. C_LIO_LIWhat did we find? Thirteen metabolites were identified as significantly different. C_LIO_LIWhat 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. C_LI