Brain-Gut Interactions in Inflammatory Bowel Disease

Abstract

Psycho-neuro-endocrine-immune modulation through the brain-gut axis likely has a key role in the pathogenesis of inflammatory bowel disease (IBD). The brain-gut axis involves interactions among the neural components, including (1) the autonomic nervous system, (2) the central nervous system, (3) the stress system (hypothalamic-pituitary-adrenal axis), (4) the (gastrointestinal) corticotropin-releasing factor system, and (5) the intestinal response (including the intestinal barrier, the luminal microbiota, and the intestinal immune response). Animal models suggest that the cholinergic anti-inflammatory pathway through an anti-tumor necrosis factor effect of the efferent vagus nerve could be a therapeutic target in IBD through a pharmacologic, nutritional, or neurostimulation approach. In addition, the psychophysiological vulnerability of patients with IBD, secondary to the potential presence of any mood disorders, distress, increased perceived stress, or maladaptive coping strategies, underscores the psychological needs of patients with IBD. Clinicians need to address these issues with patients because there is emerging evidence that stress or other negative psychological attributes may have an effect on the disease course. Future research may include exploration of markers of brain-gut interactions, including serum/salivary cortisol (as a marker of the hypothalamic-pituitary-adrenal axis), heart rate variability (as a marker of the sympathovagal balance), or brain imaging studies. The widespread use and potential impact of complementary and alternative medicine and the positive response to placebo (in clinical trials) is further evidence that exploring other psycho-interventions may be important therapeutic adjuncts to the conventional therapeutic approach in IBD.

Importance of CRF Receptor-Mediated Mechanisms of the Bed Nucleus of the Stria Terminalis in the Processing of Anxiety and Pain

“…Data represent mean±SEM, *Po0.05, and ***Po0.001 compared with SHAM þ vehicle (VEH) infusion, and þ Po0.05 and þ þ þ Po0.001 compared with WAS þ indicated infusion by two-way analysis of variance (ANOVA) with Tukey's post hoc analysis. (Bonaz and Bernstein, 2013;Myers and Greenwood-Van Meerveld, 2007)-less is known about the role of CRF in the BNST. Therefore, in the present study we aimed to investigate the role of the CRF system in the BNST AL in precipitating exaggerated anxiety and nociception following chronic intermittent psychological stress.…”

Editorial: the impact of the placebo effect in Crohn's disease

“…In the phase 2 clinical trial of Filgotinib (a JAK-1 inhibitor) in patients with moderate-severely active CD, 15% of patients randomised to placebo had an endoscopic response (defined as a >50% reduction in the simple endoscopic score for Crohn's disease: SES-CD) as early as week 10, and 7% achieved endoscopic remission at the same timepoint (defined more stringently as ES-CD ≤4, ulcerated surface subscore of 1 or less in all five bowel segments). 3 These data are surprising, especially given the severity of the disease population enrolled, with over 2/3 of patients having previously failed TNF blockers. Enrichment trial designs aim to help reduce population and treatment heterogeneity and ultimately improve efficiency.…”

"Role of Psychosocial Factors on the Course of Inflammatory Bowel Disease and Associated Psychotherapeutic Approaches. A Fresh Perspective and Review"

“…This stress induces changes in GI function, such as increased intestinal permeability and visceral sensitivity, and altered GI gut motility, which could lead to IBD symptoms [2,11,22]. Especially early life stress, such as maternal separation, has a large impact on inflammation, intestinal barrier function and dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis in rodents and animals [23]. This psychological distress is higher in IBD patients during active disease than during remission [9,24].…”

“…Psychological stress can also be a side effect of treatment, such as corticosteroids [2]. Stress induces, aggravates and influences the course of IBD occurs through its effect on the brain-gutaxis (BGA), which consists of all the connections between the brain and the gut and include the HPA axis, autonomic nervous system, central nervous system, corticotrophin-releasing factor system, and the intestinal response [11,23]. Dysregulation of the BGA contributes to the pathogenesis of IBD [11].…”

“…Additionally, the interaction between the BGA, immune system, and gut microbiota plays a role in the development of gut disorders such as IBD [11]. Gut bacteria are modified by stress but also contribute to gut motility, permeability and visceral sensitivity and may communicate with the brain [11,23]. Furthermore, many studies have focused on one component of the BGA, namely the HPA axis, which is activated by stress and may be impaired or hypo reactive in IBD patients [23].…”