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Integrated multi-omics analysis reveals a gut microbiota-tryptophan metabolism axis contributes to sex differences in a β-aminopropionitrile-induced aortic dissection mouse model - PubMed

4 hours ago
  • #Aortic Dissection
  • #Sex Differences
  • #Tryptophan Metabolism
  • Female mice were less susceptible to aortic dissection (AD) induced by β-aminopropionitrile (BAPN), showing reduced rupture rates, incidence, and aortic dilation.
  • Transcriptomic analysis indicated lower inflammation-related gene induction and immune cell infiltration in female non-dissected mice.
  • Metabolomic profiling revealed higher levels of tryptophan-indole pathway metabolites (e.g., indolepyruvate, indole-3-acetic acid) in female mice.
  • Microbiome analysis showed greater abundance of tryptophan-metabolizing Clostridium species and upregulated genes for indolepyruvate synthesis in female mice.
  • Integrated omics identified negative correlations between indole metabolites and aortic immune-inflammatory gene modules.
  • In vivo experiments demonstrated that indolepyruvate treatment delayed AD progression in male mice.
  • The study proposes a gut microbiota-tryptophan metabolism-aortic inflammation axis contributing to sex differences in AD.