Effects of Psychological Stress on Inflammatory Bowel Disease via the Microbiota–Gut–Brain Axis
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic idiopathic inflammatory disorder of the gastrointestinal tract characterized by relapsing and remitting symptoms. The disease is marked by a disturbance in the interplay between the intestinal microbiota, the gut, and the brain, collectively known as the microbiota–gut–brain axis. This axis involves complex interactions among the nervous system, the neuroendocrine system, the gut microbiota, and the host immune system. Emerging evidence suggests that psychological stress exacerbates the severity of IBD by negatively affecting this axis, leading to alterations in the hypothalamic–pituitary–adrenal (HPA) axis, the balance between the sympathetic nervous system (SNS) and vagus nerves, the homeostasis of the intestinal flora and metabolites, and normal intestinal immunity and permeability. While current evidence is insufficient, psychotropic agents, psychotherapies, and interventions targeting the microbiota–gut–brain axis show potential in improving symptoms and quality of life in IBD patients. Further research is needed to translate these findings into therapeutic approaches that enhance both physical and psychological well-being.
Introduction
IBD is a systemic disease often associated with comorbidities such as mood disorders, and there is a bidirectional relationship between psychological comorbidities and IBD. Communication between the gut and the brain is regulated by multiple pathways, including neural, hormonal, immune, metabolic, and microbial signals. Dysregulation of the gut–brain axis serves as a crucial link between gastrointestinal and neurological diseases. This review aims to discuss how psychological stress affects IBD through the microbiota–gut–brain axis.
Gut–Brain Communication
The gut–brain axis, discovered in the 21st century, is a link between the cognitive and emotional centers of the brain and intestinal functions. This communication occurs at different levels:
Neuronal Communication
The autonomic nervous system (ANS), composed of the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS, including the vagus nerve), plays a key role in gut–brain communication. Stress stimulates the SNS, activating the sympatho–adreno–medullary (SAM) axis and releasing catecholamines from the adrenal gland medulla. In contrast, the PNS, with acetylcholine as its main neurotransmitter, predominates during rest and digestion. The enteric nervous system (ENS), an independent nervous system in the gastrointestinal tract, coordinates gut functions such as motility, blood flow regulation, and epithelial secretion. The ANS integrates signals from the ENS and the central nervous system (CNS) to maintain physiological homeostasis and regulate gastrointestinal functions.
Neuroendocrine Communication
The HPA axis is a critical component of the neuroendocrine system. During stress, corticotropin-releasing hormone (CRH) from the hypothalamus promotes the release of adrenocorticotropic hormone (ACTH) from the pituitary, which targets the adrenal cortex to release glucocorticoids. These hormones prepare the body for the “fight or flight” response and play a role in gut–brain communication.
Microbial Communication
The gut microbiota, a relatively new component of the gut–brain axis, influences brain function. Changes in microbiota composition and microbial metabolites, such as short-chain fatty acids (SCFAs), can affect the central nervous system. For example, SCFAs have been shown to exert antidepressant and antianxiety effects by modulating tryptophan metabolism and neurotransmitter levels.
Involvement of the Immune System
The mucosal immune system plays a critical role in gut–brain communication. Peripheral interleukin-17-producing T cells can induce neuronal death and accelerate neurodegeneration, while the gut microbiome and microbial metabolites contribute to the transformation of mucosal T cells to the T helper 17 (Th17) phenotype, aggravating neuroinflammation.
Gut Microbiota
The gut microbiota in healthy individuals consists mainly of Firmicutes and Bacteroidetes. It plays a vital role in metabolic, immune, and protective functions. In IBD patients, there is a taxonomic shift with reduced Firmicutes and increased Bacteroides species. The abundance of Enterobacteriaceae is also elevated in CD patients. These changes are accompanied by alterations in microbial metabolites, such as reduced SCFAs, which are crucial for immune homeostasis and intestinal barrier integrity.
Stress and the Gut–Brain Axis in IBD
HPA Axis
The HPA axis is the core regulator of the stress response and significantly influences the microbiota–gut–brain axis. Stress-induced activation of the HPA axis increases cortisol secretion, which can increase intestinal permeability and trigger inflammation. Studies have shown that stress exacerbates colitis by increasing intestinal permeability and altering gut microbiota composition. Probiotics can correct stress-induced abnormalities in the colonic flora and improve intestinal barrier function by normalizing HPA axis function.
ANS
Stress disrupts the balance between the SNS and vagus nerves, promoting inflammation by inhibiting the vagus nerve and stimulating the SNS. The vagus nerve has protective effects on IBD, and vagus nerve stimulation (VNS) has been shown to reduce inflammation in animal models and CD patients. Conversely, SNS activation exacerbates IBD by promoting the release of catecholamines and increasing neutrophil infiltration.
CNS
Neuroimaging studies have revealed that psychological stress induces morphological, functional, and metabolic changes in specific brain regions in IBD patients. These changes are associated with disease severity and involve regions related to pain, emotion, and cognitive functions. The middle cingulate cortex (MCC) is particularly implicated in stress-induced exacerbation of IBD symptoms.
Stress and the Intestinal Microbiota
Stress exposure alters the composition of the gut microbiota, reducing beneficial bacteria such as Lactobacillus and increasing pathogenic bacteria. Stress also reduces the production of SCFAs, which are essential for metabolic and immune homeostasis. These changes contribute to the exacerbation of colitis.
Stress and Intestinal Immunity
Psychological stress triggers systemic and mucosal proinflammatory responses in IBD patients. Stress increases the infiltration of neutrophils, B cells, and proinflammatory macrophages in the colonic lamina propria, compromising the thymus and altering the proportions of immune cells in mesenteric lymph nodes. Stress also enhances the expression of proinflammatory cytokines such as IL-18 and IL-22, which play critical roles in mucosal immunity and barrier integrity.
Managing Stress in Patients with IBD
Psychotropic Agents and Psychotherapies
Psychotropic agents, such as antidepressants, and psychotherapies, including cognitive behavioral therapy (CBT) and mindfulness-based interventions (MBI), have shown promise in managing stress in IBD patients. Antidepressants can alleviate gastrointestinal symptoms and improve quality of life, although evidence is limited. Psychotherapies such as stress management, CBT, and hypnosis have been shown to reduce anxiety, depression, and disease activity in IBD patients.
Interventions Targeting the Microbiota–Gut–Brain Axis
Probiotics and other interventions targeting the gut microbiota have been explored as potential therapies for IBD. Probiotics such as Lactobacillus species have been shown to correct stress-induced abnormalities in the gut microbiota and improve intestinal barrier function. Other interventions, such as oxytocin, have demonstrated protective effects in stress-aggravated colitis models by reducing inflammation and improving gut barrier function.
Conclusion
Psychological stress exacerbates IBD by disrupting the microbiota–gut–brain axis, leading to alterations in the HPA axis, SNS and vagus nerve activity, gut microbiota composition, and intestinal immunity. While current evidence is limited, psychotropic agents, psychotherapies, and interventions targeting the microbiota–gut–brain axis show potential in improving symptoms and quality of life in IBD patients. Further research is needed to translate these findings into effective therapeutic approaches.
doi.org/10.1097/CM9.0000000000003389
Was this helpful?
0 / 0