Gastroenterology

Gastroenterology

Volume 144, Issue 1, January 2013, Pages 36-49
Gastroenterology

Reviews and Perspectives
Reviews in Basic and Clinical Gastroenterology and Hepatology
Brain-Gut Interactions in Inflammatory Bowel Disease

https://doi.org/10.1053/j.gastro.2012.10.003Get rights and content

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.

Section snippets

Neuroanatomical Basis of the Brain-Gut Axis

The brain and the gut communicate through the autonomic nervous system (ANS) and the circumventricular organs8 both in physiological and pathological conditions. The ANS, represented by the parasympathetic and sympathetic nervous systems (SNS), includes the vagus nerves (VNs), the sacral parasympathetic pelvic nerves, and the splanchnic nerves. These are mixed nerves containing afferent fibers (90% for VNs and 50% for sympathetic nerves) and efferent fibers facilitating neurotransmission

Stress and the CRFergic system

Stress is the response of the organism to a solicitation of the environment.10 The reaction of stress is physiologic but may become pathologic in the case of an imbalance between the capacities of adaptation and the requirement of the environment, leading to functional, metabolic, and even lesional disorders.11 The HPA axis is the classic pathway through which stress induces an adaptation. Corticotropin-releasing factor (CRF), the principal neuromediator of stress, directly administered into

Altered Psychological Functioning Before and After Diagnosis of IBD

Whether or not depression and anxiety actually have an effect on the inflammatory state in IBD and secondarily on disease expression, it is well known from community studies that a great deal of the functional impairment and disability associated with health conditions is related to the presence of anxiety or depression.82, 83, 84 Subjects with more depressive symptoms exhibit enhanced inflammation to a stressor compared with those with fewer depressive symptoms.85 Individuals with IBD have

Translational Implications With Therapeutic Applications Through the Brain-Gut Axis

Anti-TNF therapy is the gold standard in the treatment of patients with moderate to severe IBD.145 An alternative therapy to conventional anti-TNF treatment, based on brain-gut interactions, is stimulation of the cholinergic anti-inflammatory pathway, either pharmacologically or through VNS or nutrition (Figure 4).

Conclusion

Increasing knowledge gained from animal models exploring the brain-gut axis has provided potential insight into the management of IBD in humans. Depression and stress may both result from active IBD but may also play a role in triggering or magnifying symptoms in patients with IBD. The important symptoms of pain and fatigue, frequently reported by patients with IBD,163 are affected by a patient's mental health. Completely abrogating the inflammatory state may not eliminate these symptoms.164,

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    Conflicts of interest The authors disclose no conflicts.

    Funding Dr Bernstein is supported in part by the Bingham Chair in Gastroenterology. He has served as a consultant to Abbott Canada, Janssen Canada, Shire Canada, Vertex Pharmaceuticals, and Bristol-Myers Squibb and has received a research grant from Abbott Canada and an educational grant from Aptalis Pharmaceuticals. Dr Bonaz has served as a consultant to Abbott France, Almirall France, Cephalon France, Ferring France, MSD France, and Otsuka Pharmaceutical France.

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