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

Biochim Biophys Acta Mol Basis Dis. 2021 Dec 1;1867(12):166266. doi: 10.1016/j.bbadis.2021.166266. Epub 2021 Sep 2.

Abstract

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.

Keywords: Correlation network; Diabetes; Metabolomics; Microbiome; Sex difference.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology
  • Fatty Acids, Volatile / genetics*
  • Fatty Acids, Volatile / metabolism
  • Female
  • Gastrointestinal Microbiome / genetics*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Metabolome / genetics*
  • Metabolomics
  • Mice
  • Mice, Inbred NOD / genetics
  • Mice, Inbred NOD / metabolism
  • Sex Characteristics

Substances

  • Fatty Acids, Volatile