Chronic stress at the crossroads: Decoding the HPA-SAM-immune-gut axis in inflammatory bowel disease pathogenesis and therapeutics.

Stress, a prevalent factor in modern life, profoundly impacts human health by disrupting immune function and intestinal homeostasis. This review elucidates the mechanisms through which stress dysregulates the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal medulla (SAM) axes, leading to altered glucocorticoid and catecholamine levels that impair immune responses and promote inflammation. Chronic stress exacerbates gut microbiota dysbiosis, reduces microbial diversity, and compromises intestinal barrier integrity, contributing to conditions like inflammatory bowel disease (IBD). Stress-induced HPA axis dysfunction and neuroendocrine alterations further aggravate IBD pathogenesis by enhancing pro-inflammatory pathways (e.g., IL-6/STAT3) and disrupting mucosal immunity. Clinical evidence highlights bidirectional links between psychological stress and IBD progression, with stress exacerbating symptoms and IBD increasing susceptibility to anxiety and depression. Therapeutic strategies, including probiotics, anti-inflammatory agents, and psychological interventions (e.g., yoga), show promise in mitigating stress-related gut inflammation and improving patient outcomes. This synthesis underscores the necessity of integrating psychological care with conventional treatments to address the multifaceted interplay between stress, immunity, and gut health in IBD management.