Understanding neuroimmune interactions in disorders of gut–brain interaction: from functional to immune-mediated disorders

Abstract

Functional gastrointestinal disorders—recently renamed into disorders of gut–brain interaction—such as irritable bowel syndrome and functional dyspepsia are highly prevalent conditions with bothersome abdominal symptoms in the absence of structural abnormalities. While traditionally considered as motility disorders or even psychosomatic conditions, our understanding of the pathophysiology has evolved significantly over the last two decades. Initial observations of subtle mucosal infiltration with immune cells, especially mast cells and eosinophils, are since recently being backed up by mechanistic evidence demonstrating increased release of nociceptive mediators by immune cells and the intestinal epithelium. These mediators can activate sensitised neurons leading to visceral hypersensitivity with bothersome symptoms. The interaction between immune activation and an impaired barrier function of the gut is most likely a bidirectional one with alterations in the microbiota, psychological stress and food components as upstream players in the pathophysiology. Only few immune-targeting treatments are currently available, but an improved understanding through a multidisciplinary scientific approach will hopefully identify novel, more precise treatment targets with ultimately better outcomes.

Novel insights in the pathophysiology and management of functional dyspepsia

“…evidence is largely lacking (23,24). Moreover, the results of duodenal eosinophil counts are highly variable across studies and the largest study to date in 178 patients failed to confirm increased duodenal eosinophil counts even if this study could be criticized for selecting mainly older, male patients based on the outdated Rome II criteria (25).…”

The impact of acute and chronic stress on gastrointestinal physiology and function: a microbiota–gut–brain axis perspective

“…Disorders of gut-brain interaction including IBS. DGBI, many of which previously fell under the umbrella of functional GI disorders (Vanuytsel et al, 2023), are experienced by more than 40% of people worldwide (Asnicar et al, 2021). They are characterised by GI symptoms which may present as any combination of motility disturbances, visceral hypersensitivity, altered mucosal and immune function, gut microbiota and/or central nervous system processing (Schmulson & Drossman, 2017).…”

Treating disorders of brain–gut interaction with multidisciplinary integrated care. Moving towards a new standard of care

“…The pathophysiology of DBGI is not completely understood. However, repeated studies have shown the importance of neuroimmune function and its interaction with luminal microbiota and subsequent impacts on visceral sensitivity and motility 10 . This complex interplay is modulated by psychological state, personality type, and previous life events.…”

“…However, repeated studies have shown the importance of neuroimmune function and its interaction with luminal microbiota and subsequent impacts on visceral sensitivity and motility. 10 This complex interplay is modulated by psychological state, personality type, and previous life events. Psychological contributors may be a predisposing, triggering, or perpetuating element, or considered co‐morbid pathology with shared risk factors.…”