Functional Dyspepsia: Current Understanding and Future Perspective

Abstract

<b><i>Background:</i></b> Functional dyspepsia (FD) is a common disorder characterized by chronic or recurrent upper abdominal pain or discomfort without any structural abnormalities in the gastrointestinal tract. FD is categorized into two subgroups based on symptoms: postprandial distress syndrome (PDS) and epigastric pain syndrome. <b><i>Summary:</i></b> The pathophysiology of FD involves several mechanisms. Delayed gastric emptying is observed in approximately 30% of FD patients but does not correlate with symptom patterns or severity. Impaired gastric accommodation is important in the pathophysiology, particularly for PDS. Visceral hypersensitivity, characterized by heightened sensitivity to normal activities, contributes to the perception of discomfort or pain in FD. Alterations to the duodenal mucosa, including impaired mucosal barrier function and low-grade inflammation, are also implicated in the pathogenesis of FD. Microbial dysbiosis and psychological factors such as stress can further exacerbate symptoms. Treatment options include dietary modifications, establishing a physician-patient relationship, acid suppressants, prokinetics, neuromodulators, and behavioral therapies. Dietary recommendations include eating smaller, more frequent meals, and avoiding trigger foods. Acid suppressants are used as the first-line treatment. Prokinetics and neuromodulators aim to improve gastric motility and central pain processing, respectively. Behavioral therapies, including cognitive behavioral therapy and hypnotherapy, have shown benefits for refractory FD. Severe and refractory cases may require combination therapies or experimental treatments. <b><i>Key Messages:</i></b> FD is a disorder of gut-brain interaction involving diverse pathophysiological mechanisms. Individualized treatment based on symptoms and responses to interventions is crucial. Further research is needed to improve the understanding of FD and advance the development of effective therapies.

Electroacupuncture improves low-grade duodenal inflammation in FD rats by reshaping intestinal flora through the NF-κB p65/NLRP3 pyroptosis pathway

“…Researchers investigating duodenal mucosal changes in FD have shifted their focus from motor to low-grade inflammation, including duodenal mucosal permeability and eosinophil infiltration. Several studies have found that EA has beneficial effects on the gastrointestinal motility of individuals with FD [ 23 ]. We found that EA increased the gastric emptying rate and the small intestinal propulsion rate in FD model rats established by multi-factor stress intervention.…”

The Association between Functional Dyspepsia and Metabolic Syndrome—The State of the Art

“…Within this context, we can consider the development, recurrence, and persistence of FD symptoms. These symptoms depend on complex circuits involving the interaction of the gut microbial contents, epithelial cell permeability, gut wall immune cell infiltration, mediators released from the gut nerves, and systemic stress-related mechanisms [97]. Unhealthy eating habits and other unhealthy behaviors caused by long-term psychological stress have an impact on the development of gut dysbiosis and the impairment of the GI system's motility and epithelium permeability, which results in increased inflammation, leading to abdominal obesity, MetS, and illnesses like FD.…”

Putting Functional Gastrointestinal Disorders within the Spectrum of Inflammatory Disorders Can Improve Classification and Diagnostics of These Disorders

“…Recognition of FGIDs has expanded in recent years thanks to the ROME classification, which is based on the clustering of symptoms, but the pathogenesis of these disorders remains unclear [ 70 , 71 ]. As potential pathophysiology factors, visceral hypersensitivity, dysfunctional gut motility, post-infectious gastroenteritis, increased intestinal permeability, altered gut microbiota, irregular gut–brain connection, and chronic low-grade intestinal mucosal inflammation, have been recognized [ 72 , 73 , 74 , 75 , 76 , 77 ]. They are also characterized by a high prevalence of mental comorbidities and chronic pain problems, which explains a relationship between the gastrointestinal tract and the brain (the gut–brain axis) for which reason these disorders have, in recent times, been considered gut–brain interaction disorders [ 74 , 78 ].…”

“…FD is the most prevalent FGID, with a prevalence of 20% to 40%, accounting for 3% to 5% of primary care visits. People with FD have a poor quality of life due to persistent or recurring upper abdomen pain or discomfort which may be compared with that of patients with moderate heart failure [ 75 ]. Using the Rome IV criteria, FD can be classified as postprandial distress syndrome (PDS) or epigastric pain syndrome (EPS), with possible overlapping.…”

“…The immune cells causing low-grade mucosal inflammation are the ones that identify them. The enhanced permeability of the duodenal mucosa and weakened epithelial barrier are the results of inflammatory cells' release of histamine, tryptase, and cytokines, which modify submucosal afferent neurons [75,[105][106][107].…”