Summary:
This study is a narrative review that looks at and describes how stress is a physiological and psychological response that can be either adaptive or harmful depending on duration. Short-term stress can enhance performance and survival through coordinated neuroendocrine and immune responses. In contrast, prolonged or repeated stress is associated with the development and progression of multiple diseases. Individual responses to stress vary and are influenced by factors such as genetics, diet, sleep, and social support. Stress activates key biological systems, particularly the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. Activation produces a “fight-or-flight” response, characterised by increased heart rate, blood pressure, and energy mobilisation. However, chronic activation can lead to immune dysregulation, including reduced immune cell function and increased production of proinflammatory cytokines. This persistent inflammatory state is implicated in a range of conditions, including cardiovascular, gastrointestinal, autoimmune, and psychiatric disorders. The study discusses the role of the gastrointestinal microbiome in mediating the effects of stress. The gut microbiome plays a key role in nutrient metabolism, immune function, and maintenance of the intestinal barrier. Disruption of this system, known as dysbiosis, has been associated with several chronic diseases. Stress has been shown to alter the composition of the gut microbiome, increase intestinal permeability, and promote the release of inflammatory mediators. The authors discuss that chronic stress and gut microbiome disruption interact in a bidirectional manner. Stress-induced changes in immune and neuroendocrine function can alter the microbiome, while microbiome changes can further amplify stress responses. This creates a feedback loop that promotes ongoing inflammation and contributes to disease development. Overall, this study suggests that interactions between stress, immune function, and the gut microbiome are important in understanding the biological pathways underlying stress-related disease.
Abstract:
There is growing interest in understanding the complex relationship between psychosocial stress and the human gastrointestinal microbiome (GIM). This review explores the potential physiological pathways connecting these two and how they contribute to a proinflammatory environment that can lead to the development and progression of the disease. Exposure to psychosocial stress triggers the activation of the sympathetic nervous system (SNS) and hypothalamic-pituitary axis (HPA), leading to various physiological responses essential for survival and coping with the stressor. However, chronic stress in susceptible individuals could cause sustained activation of HPA and SNS, leading to immune dysregulation consisting of redistribution of natural killer (NK) cells in the bloodstream, decreased function of T and B cells, and elevation of proinflammatory cytokines such as interleukin-1, interleukin-6, tumor necrotic factor-α, interferon-gamma. It also leads to disruption of the GIM composition and increased intestinal barrier permeability, contributing to GIM dysbiosis. The GIM dysbiosis and elevated cytokines can lead to reciprocal effects and further stimulate the HPA and SNS, creating a positive feedback loop that results in a proinflammatory state underlying the pathogenesis and progression of stress-associated cardiovascular, gastrointestinal, autoimmune, and psychiatric disorders. Understanding these relationships is critical for developing new strategies for managing stress-related health disorders.
Article Publication Date: 12/2025
DOI: 10.1152/japplphysiol.00652.2024
