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References: Stress and the Gut

  1. 17.6 The Adrenal Glands - OpenStax, Anatomy and Physiology 2e (CC BY 4.0) - Free open textbook section on the adrenal cortex and medulla, the HPA axis, fight-or-flight, the general adaptation syndrome, and cortisol's effects on fuel and inflammation. The best starting point for Sections 7.3 to 7.7.

  2. Cortisol Test - MedlinePlus, US National Library of Medicine - A plain-language page on what cortisol does, how ACTH controls it, its daily rhythm (highest in the morning), and why both high and low cortisol can be serious.

  3. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress - Smith SM, Vale WW. Dialogues in Clinical Neuroscience, 2006 - An open-access review of the HPA axis, CRH (CRF), and glucocorticoid negative feedback. Source for the cascade and feedback in Sections 7.4 and 7.6.

  4. Role of Corticotropin-releasing Factor Signaling in Stress-related Alterations of Colonic Motility and Hyperalgesia - Taché Y, Million M. Journal of Neurogastroenterology and Motility, 2015 - Review of how CRF and its receptors in the brain and colon speed up colon movement and raise pain sensitivity in animals, and why CRF1-blocking drugs haven't yet become treatments.

  5. Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome - Fukudo S, Nomura T, Hongo M. Gut, 1998 - Small human study (10 people with IBS, 10 controls) showing that CRH increases colon movement, more so in IBS.

  6. Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism - Vanuytsel T, et al. Gut, 2014 - Two small experiments in healthy volunteers showing that public-speaking stress and CRH raise small-intestine permeability, blocked by a mast cell stabilizer. The data in Your Gut Check come from its abstract.

  7. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome - Barbara G, et al. Gastroenterology, 2004 - Tissue study of 44 people with IBS linking mast cells close to gut nerves with pain severity. A preview of Chapter 8.

  8. A prospective population-based study of triggers of symptomatic flares in IBD - Bernstein CN, et al. American Journal of Gastroenterology, 2010 - Year-long study of 704 people with IBD in Manitoba finding that high perceived stress, but not NSAIDs, antibiotics, or infections, was linked to flares.

  9. Crohn's Disease: Symptoms and Causes - National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) - The US government's plain-language page on Crohn's disease symptoms and the factors doctors think contribute to it.

  10. The brain-gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based study - Koloski NA, et al. Gut, 2012 - Australian study following about 1,000 adults for 12 years, showing that anxiety predicted new gut disorders and gut disorders predicted later anxiety and depression.

  11. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice - Sudo N, et al. Journal of Physiology, 2004 - The germ-free mouse study analyzed in this chapter's claim box. The free full text includes group sizes and funding.

  12. Effect of Brain-Gut Behavioral Treatments on Abdominal Pain in Irritable Bowel Syndrome: Systematic Review and Network Meta-Analysis - Goodoory VC, et al. Gastroenterology, 2024 - Combines 42 randomized trials (5,220 participants) of CBT, hypnotherapy, and related therapies for IBS pain. The source for "What's new in research" in the At the Bedside case.