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.

1 型糖尿病 (T1D) 的发病和发展过程中存在性别二态性，但其潜在的病理机制尚不清楚。在本研究中，我们通过 16S rRNA 基因测序和基于核磁共振 (NMR) 的代谢组学方法检查了 T1D 小鼠肠道微生物群和宿主代谢组的性别特异性变化，旨在研究肠道微生物群-宿主的潜在机制T1D 性别二态性中的代谢相互作用。我们的结果表明，在 T1D 的发展过程中，雌性小鼠的肠道微生物群发生了比雄性小鼠更大的变化；然而，宿主代谢组对雄性小鼠的 T1D 更敏感。相关网络分析表明，T1D 诱导的宿主代谢变化可能受肠道微生物群以性别特异性方式调节，主要涉及短链脂肪酸（SCFAs）代谢、能量代谢、氨基酸代谢和胆碱代谢。因此，我们的研究表明，性别依赖性的“肠道微生物群-宿主代谢轴”可能与 T1D 的性别二态性有关，微生物与代谢物之间的联系可能有助于 T1D 的预防和治疗。