Stress and the Autoimmune System

​Stress plays a significant role in triggering and worsening autoimmune diseases by disrupting the body’s immune regulation. Chronic stress activates the hypothalamic-pituitary-adrenal (HPA) axis, leading to sustained release of cortisol and other hormones that can dysregulate immune cells and promote inflammation. Prolonged stress elevates pro-inflammatory cytokines, such as those driving rheumatoid arthritis and psoriasis flares, while altering T-cell balances. This creates a feedback loop where immune overactivity heightens inflammation, making the body attack its own tissues more aggressively. 
 
HPA axis dysregulation from stress also weakens immune self-regulation, increasing susceptibility in genetically predisposed individuals; studies link stress disorders like PTSD to 36-46% higher autoimmune risk. Up to 80% of patients report major stress before disease onset, with cohort data showing stressed individuals develop autoimmune conditions at rates of 9.1 per 1,000 person-years versus 6.0 in controls. Traumatic stress exacerbates symptoms in diseases like lupus via neuroendocrine changes that amplify cytokine production.
 
The gut microbiome acts as a critical mediator between stress and autoimmunity by influencing immune regulation through bidirectional signaling along the gut-brain axis. Dysbiosis from stress disrupts this balance, promoting inflammation that can trigger or exacerbate autoimmune responses. Stress activates the HPA axis and sympathetic nervous system, altering gut permeability and microbial composition, favouring pro-inflammatory bacteria like Bilophila while reducing diversity. This dysbiosis elevates cytokines, boosts effector T helper cells, and impairs self-tolerance, creating a feedback loop that sustains inflammation linked to diseases like multiple sclerosis or rheumatoid arthritis. Conversely, dysbiotic microbiota signal back to the brain via the vagus nerve or metabolites (e.g., short-chain fatty acids), amplifying HPA activity and cortisol resistance, which further weakens immune barriers and promotes Th17-driven autoimmunity. Human studies associate stress-induced dysbiosis with higher autoimmune risk in susceptible individuals, underscoring probiotics or diet as potential interventions.
 
References
Chaudhary, R., Prasad, A., Agarwal, V., Rehman, M., Kumar, A. et al. (2023, December). Chronic Stress Predisposes to the Aggravation of Inflammation in Autominnune Diseases with Focus on Rheumatoid Arthritis and Psoriasis.International Immunopharmacology.
 
Ewers, K. (2021, August 10). Stress, Trauma, and Dybiosis: Connecting the Gut-Brain Axis to Autoimmune Disease. The Institute for Functional Medicine.
 
Marwaha, K., Coin, R., Asmis, K., Czaplinski, K., Holland, N., et al. (2024). Exploring the Complex Relationship Between Psychological Stress and the Gut Microbiome: Implications for Inflammation and Immune Modulation. Journal of Applied Physiology.
 
Rea, K., Dinan, T.G. & Cryan, J.F. (2016, March 4). The Microbiome: A Key Regulator of Stress and Neuroinflammation. Neurobiology of Stress.
 
Song, H., Fang, F., Tomasson, G., et al. (2018). 319; (23): 2388-2400. Association of Stress-Related Disorders with Subsequent Autoimmune Disease. JAMA. 
 
Werbner, M., Barsheshet, Y., Werbner, N., Zigdon, M., Averbuch, I., et al. (2019, May 14). Social-Stress- Responsive Microbiota Induces Stimulation of Self-Reactive Effector T Helper Cells. mSystems Journal.
 
(2026). Stress & Autoimmune Disease: Navigating the Complex Relationship. Global Autoimmune Institute.
 
(2025). The Link Between Stress and Autoimmune Flare-ups. Sanitas Medical Center. https://www.mysanitas.com/en/blog/link-between-stress-and-autoimmune-flare-ups-0
 
(2019, May 14). How Stressed-Out Gut Bacteria May Trigger Autoimmune Response. Neuroscience News.Com. https://neurosciencenews.com/stress-microbiota-autoimmune-13092/