Understanding the Connection between Gut Homeostasis and Psychological Stress

J Nutr. 2023 Apr;153(4):924-939. doi: 10.1016/j.tjnut.2023.01.026. Epub 2023 Jan 31.


Long-term exposure to adverse life events that provoke acute or chronic psychological stress (hereinafter "stress") can negatively affect physical health and even increase susceptibility to psychological illnesses, such as anxiety and depression. As a part of the hypothalamic-pituitary-adrenal axis, corticotropin-releasing factor (CRF) released from the hypothalamus is primarily responsible for the stress response. Typically, CRF disrupts the gastrointestinal system and leads to gut microbiota dysbiosis, thereby increasing risk of functional gastrointestinal diseases, such as irritable bowel syndrome. Furthermore, CRF increases oxidative damage to the colon and triggers immune responses involving mast cells, neutrophils, and monocytes. CRF even affects the differentiation of intestinal stem cells (ISCs), causing enterochromaffin cells to secrete excessive amounts of 5-hydroxytryptamine (5-HT). Therefore, stress is often accompanied by damage to the intestinal epithelial barrier function, followed by increased intestinal permeability and bacterial translocation. There are multi-network interactions between the gut microbiota and stress, and gut microbiota may relieve the effects of stress on the body. Dietary intake of probiotics can provide energy for ISCs through glycolysis, thereby alleviating the disruption to homeostasis caused by stress, and it significantly bolsters the intestinal barrier, alleviates intestinal inflammation, and maintains endocrine homeostasis. Gut microbiota also directly affect the synthesis of hormones and neurotransmitters, such as CRF, 5-HT, dopamine, and norepinephrine. Moreover, the Mediterranean diet enhances the stress resistance to some extent by regulating the intestinal flora. This article reviews recent research on how stress damages the gut and microbiota, how the gut microbiota can improve gut health by modulating injury due to stress, and how the diet relieves stress injury by interfering with intestinal microflora. This review gives insight into the potential role of the gut and its microbiota in relieving the effects of stress via the gut-brain axis.

Keywords: corticotropin-releasing factor (CRF); hypothalamus–pituitary–adrenal (HPA) axis; intestinal damage; probiotics; stress.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Corticotropin-Releasing Hormone* / metabolism
  • Homeostasis
  • Hypothalamo-Hypophyseal System* / metabolism
  • Hypothalamo-Hypophyseal System* / microbiology
  • Pituitary-Adrenal System / metabolism
  • Serotonin
  • Stress, Psychological


  • Corticotropin-Releasing Hormone
  • Serotonin