Sex-dependent effects on the gut microbiota and host metabolome in type 1 diabetic mice

Sexual dimorphism exists in the onset and development of type 1 diabetes (T1D), but its potential pathological mechanism is poorly understood. In the present study, we examined sex-specific changes in the gut microbiome and host metabolome of T1D mice via 16S rRNA gene sequencing and nuclear magnetic resonance (NMR)-based metabolomics approach, and aimed to investigate potential mechanism of the gut microbiota-host metabolic interaction in the sexual dimorphism of T1D. Our results demonstrate that female mice had a greater shift in the gut microbiota than male mice during the development of T1D; however, host metabolome was more susceptible to T1D in male mice. The correlation network analysis indicates that T1D-induced host metabolic changes may be regulated by the gut microbiota in a sex-specific manner, mainly involving short-chain fatty acids (SCFAs) metabolism, energy metabolism, amino acid metabolism, and choline metabolism. Therefore, our study suggests that sex-dependent gut microbiota-host metabolism axis may be implicated in the sexual dimorphism of T1D, and the link between microbes and metabolites might contribute to the prevention and treatment of T1D.

Automated summary

The study reveals sexual dimorphism in T1D mice, with female mice showing greater changes in gut microbiota and male mice being more susceptible to T1D in terms of host metabolome. The correlation network analysis suggests that T1D-induced host metabolic changes may be regulated by the gut microbiota in a sex-specific manner, involving SCFAs metabolism, energy metabolism, amino acid metabolism, and choline metabolism.