The Gut Microbiome Regulates Psychological-Stress-Induced Inflammation

Chunliang Xu, Sung Kyun Lee, Dachuan Zhang, Paul S. Frenette

Research output: Contribution to journalArticlepeer-review

81 Scopus citations


Psychological stress has adverse effects on various human diseases, including those of the cardiovascular system. However, the mechanisms by which stress influences disease activity remain unclear. Here, using vaso-occlusive episodes (VOEs) of sickle cell disease as a vascular disease model, we show that stress promotes VOEs by eliciting a glucocorticoid hormonal response that augments gut permeability, leading to microbiota-dependent interleukin-17A (IL-17A) secretion from T helper 17 (Th17) cells of the lamina propria, followed by the expansion of the circulating pool of aged neutrophils that trigger VOEs. We identify segmented filamentous bacteria as the commensal essential for the stress-induced expansion of aged neutrophils that enhance VOEs in mice. Importantly, the inhibition of glucocorticoids synthesis, blockade of IL-17A, or depletion of the Th17 cell-inducing gut microbiota markedly reduces stress-induced VOEs. These results offer potential therapeutic targets to limit the impact of psychological stress on acute vascular occlusion.

Original languageEnglish
Pages (from-to)417-428.e4
Issue number2
StatePublished - 18 Aug 2020
Externally publishedYes


  • IL-17A
  • Th17
  • glucocorticoid
  • gut-brain axis
  • hypothalamic-pituitary-adrenal axis
  • microbiota
  • segmented filamentous bacteria
  • sickle cell disease
  • stress
  • vaso-occlusion


Dive into the research topics of 'The Gut Microbiome Regulates Psychological-Stress-Induced Inflammation'. Together they form a unique fingerprint.

Cite this