Immunopathological and molecular basis of functional dyspepsia and current therapeutic approaches

ABSTRACT

Introduction: Functional dyspepsia (FD) is widespread with 20% prevalence worldwide and a significant economic burden due to health care cost and constraints on daily activities of patients. Despite extensive investigation, the underlying causes of dyspepsia in a majority of patients remain unknown. Common complaints include abdominal discomfort, pain, burning, nausea, early satiety, and bloating. Motor dysfunction of the gut was long considered a major cause, but recent investigations suggest immune-based pathophysiological and molecular events in the duodenum are more probable contributing factors.

Areas Covered: Inflammatory mediators and immune cells including duodenal eosinophils, intraepithelial lymphocytes, and T-cells have been implicated in the underlying cause of disease process, as have genetic factors. In this article, we critically reviewed findings, identified gaps in knowledge and suggested future directions for further investigation to identify targets and develop better therapeutic approaches.

Expert commentary: Impaired gastric accommodation, slow gastric emptying, and increased visceral sensitivity have long been thought of as main causal factors of FD. However, more recent identification of eosinophilic degranulation and recruitment of T cells that induce mild duodenal inflammation are giving rise to new insights into immune-mediated pathophysiology. These insights offer promising avenues to explore for immune-mediated therapy in the future.

KEYWORDS:

• Functional dyspepsia
• dyspepsia
• endoscopy
• duodenal inflammation
• eosinophil degranulation
• H. pylori

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The research work of DK Agrawal is supported by research grants R01HL120659, R01 HL128063, and R01HL144125 from the National Institutes of Health, USA. The content of this review article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.