Interrogating the Gut-Brain Axis in the Context of Inflammatory Bowel Disease: A Translational Approach

Stephen M Collins, Stephen M Collins

Abstract

This review examines preclinical and clinical studies relevant to our understanding of how the bidirectional gut-brain axis influences the natural history of inflammatory bowel disease. Preclinical studies provide proof of concept that preexisting behavioral illness, such as depression, results in increased susceptibility to inflammatory stimuli and that commonly used classes of antidepressants protect against this vulnerability. However, clinical studies suggesting behavioral illness as a risk factor for IBD and a protective role for antidepressants have relied primarily on symptom-reporting rather than objective measurements of inflammation. In terms of gut-to-brain signaling, there is emerging evidence from preclinical and clinical observation that intestinal inflammation alters brain functions, including the induction of mood disorders, alteration of circadian rhythm both centrally and peripherally, and changes in appetitive behaviors. Furthermore, preclinical studies suggest that effective treatment of intestinal inflammation improves associated behavioral impairment. Taken together, the findings of this review encourage a holistic approach to the management of patients with IBD, accommodating lifestyle issues that include the avoidance of sleep deprivation, optimized nutrition, and the monitoring and appropriate management of behavioral disorders. The review also acknowledges the need for better-designed clinical studies evaluating the impact of behavioral disorders and their treatments on the natural history of IBD, utilizing hard end points to assess changes in the inflammatory process as opposed to reliance on symptom-based assessments. The findings of the review also encourage a better understanding of changes in brain function and circadian rhythm induced by intestinal inflammation.

Keywords: antidepressants; circadian rhythm; cytokines; depression; inflammation; vagus nerve.

© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.

Figures

FIGURE 1.
FIGURE 1.
The structure of this review is illustrated. It will address 6 questions pertaining to the role of the bidirectional gut-brain axis in the natural history of IBD. Each question is addressed by first examining evidence of biologic feasibility based on preclinical studies, followed by a review of the existing clinical literature pertinent to the question.
FIGURE 2.
FIGURE 2.
Bidirectional gut-brain interactions in IBD may lead to a vicious cycle that promotes intestinal inflammation and reduces well-being. Thus, a holistic approach to the management of IBD is encouraged, involving both gut-to-brain and brain-to-gut signaling.

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Source: PubMed

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