The Gut-Brain Axis in Inflammatory Bowel Disease—Current and Future Perspectives

Abstract

The gut–brain axis is a bidirectional communication system driven by neural, hormonal, metabolic, immunological, and microbial signals. Signaling events from the gut can modulate brain function and recent evidence suggests that the gut–brain axis may play a pivotal role in linking gastrointestinal and neurological diseases. Accordingly, accumulating evidence has suggested a link between inflammatory bowel diseases (IBDs) and neurodegenerative, as well as neuroinflammatory diseases. In this context, clinical, epidemiological and experimental data have demonstrated that IBD predisposes a person to pathologies of the central nervous system (CNS). Likewise, a number of neurological disorders are associated with changes in the intestinal environment, which are indicative for disease-mediated gut–brain inter-organ communication. Although this axis was identified more than 20 years ago, the sequence of events and underlying molecular mechanisms are poorly defined. The emergence of precision medicine has uncovered the need to take into account non-intestinal symptoms in the context of IBD that could offer the opportunity to tailor therapies to individual patients. The aim of this review is to highlight recent findings supporting the clinical and biological link between the gut and brain, as well as its clinical significance for IBD as well as neurodegeneration and neuroinflammation. Finally, we focus on novel human-specific preclinical models that will help uncover disease mechanisms to better understand and modulate the function of this complex system.

Are neurodegenerative diseases associated with an increased risk of inflammatory bowel disease? A two-sample Mendelian randomization study

“…Increasing evidence has shown that the gut-brain axis is pivotal in connecting neurological and gastrointestinal diseases. This communication system, driven by neural, hormonal, immunological, microbial, metabolic, and other signals, is expected to provide a new perspective for explaining the relationship between IBD and neurodegenerative diseases ( 5 ). For example, a cohort study based on the Korean population suggested that patients with IBD had a higher risk of neurodegenerative diseases (Parkinson’s disease [PD] and Alzheimer’s disease [AD]) than non-IBD controls ( 6 ).…”

Cerebral hemodynamic changes to transcranial Doppler sonography in celiac disease: A pilot study

“…Recent molecular findings have also proposed the role of some soluble inflammatory factors from the gut damaged mucosa across the gut–epithelial barrier and the blood–brain barrier as relevant components for both functional and structural changes at the brain level. Namely, it has been widely documented that neuroinflammatory phenomena negatively impact both emotional behavior and cognition ( Crupi et al, 2010 ; Günther et al, 2021 ), thus adding further support to the relationship between CD, neuropsychiatry, and neuroinflammation. This evidence underlines the need for an early diagnosis and full adherence to the GFD to limit, or even prevent, the neuropsychiatric and neurological involvement in CD and its complications ( Hadjivassiliou et al, 2019 ).…”

Preserved central cholinergic functioning to transcranial magnetic stimulation in de novo patients with celiac disease

“…Of note, accumulating evidence has suggested that some inflammatory soluble factors derived from the inflamed intestinal mucosa across the gut–epithelial barrier and the blood–brain barrier are major factors for structural and functional alterations in the CNS. In particular, neuroinflammation has been shown to exert detrimental effects on both cognition and emotional behavior [ 72 , 73 ], thus supporting the link between neuroinflammatory, neurological, and psychiatric manifestations in CD. Translationally, these findings highlight the importance of a prompt diagnosis, clinical awareness, and compliance to an adherent GFD to prevent, or at least limit, the neurological and neuropsychiatric involvement in CD and the related disease progression [ 7 ].…”