A pathophysiologic framework for the overlap of disorders of gut-brain interaction and the role of the gut microbiome

Abstract

The International Rome Committee defines Disorders of Gut-Brain Interactions (DGBI) based upon distinct combinations of chronic and/or recurrent unexplained gastrointestinal symptoms. Yet patients often experience overlapping DGBI. Patients with DGBI frequently also suffer from extraintestinal symptoms, including fatigue, sleep disturbances, anxiety, and depression. Patients with overlapping DGBI typically experience more severe GI symptoms and increased psychosocial burden. Concerning the pathophysiology, DGBI are associated with disruptions in gut motility, function of the brain and enteric neurons, immune function, and genetic markers, with recent findings revealing gut microbiome alterations linked to these mechanisms of DGBI. Emerging evidence summarized in this review suggests that the microbiome influences various established disease mechanisms of different DGBI groups. Overall, changes in the gastrointestinal microbiome do not seem to be linked to a specific DGBI subgroup but may play a key role in the manifestation of different DGBI and, subsequently, overlap of DGBI. Understanding these shared mechanisms and the role of the gastrointestinal microbiome, particularly for overlapping DGBI, might aid in developing more precise diagnostic criteria and treatment strategies while developing personalized interventions that target specific mechanisms to improve patient outcomes.

Keywords: Microbiome; disorders of gut-brain interactions; gastrointestinal motility; genes; gut-brain axis; immune function; mind; neurofunction.

Figure 1.

Schematic representations of key factors related to the microbiome that influence gut-brain interactions. direct effects of the gut microbiome on a) brain function via the production of neurotransmitters like serotonin, dopamine, and GABA or short-chain fatty acids that regulate neurotransmitter production. b) effects on gastrointestinal motility and sensory function mediated by specific microbial products (e.g., acetate, propionate, and butyrate) that alter neurotransmitter release. c) altered immune function with bacteria colonizing the gastrointestinal mucosa influencing regulatory T cells (tregs) and immunoglobulin-producing B cells. Immune mediators such as cytokines have central and peripheral subsequent influence, e.g., visceral sensory function. indirect effects of the gut microbiome: a) the activation of the immune system, via release of proinflammatory cytokines, influences the central processing of visceral afferents, but also by sensitizing peripheral pathways. Dysregulation of cytokine signaling has been implicated in depression and anxiety and is associated with cognitive impairment, mood disorders, and neuroinflammation. b) bacterial metabolites can impact signaling pathways in epithelial cells, leading to changes in the expression of genes associated with inflammation, barrier function, and pain perception. c) in relation to psychological stress, interventions that target the gut microbiome, such as probiotics and dietary changes, have been shown to affect stress-related symptoms.