What Causes Functional Gastrointestinal Disorders? A Proposed Disease Model

Area of Science:

• Gastroenterology
• Immunology
• Pathology

Background:

• Over 20% of Americans experience chronic gastrointestinal symptoms, including Irritable Bowel Syndrome (IBS) and Functional Dyspepsia (FD).
• Current Rome IV classification categorizes IBS and FD as functional gastrointestinal disorders, implying a lack of identifiable pathology.
• Emerging research suggests underlying immune activation and subtle intestinal pathology in subsets of patients with FD and IBS-diarrhea.

Purpose of the Study:

• To propose a revised disease model for IBS and FD that incorporates immune activation and intestinal pathology.
• To explain the diverse symptoms, food-related triggers, and overlap with other conditions like GERD.
• To lay the groundwork for future pathology-based subtyping and targeted therapies.

Main Methods:

• Review of emerging evidence on immune activation and intestinal pathology in functional gastrointestinal disorders.
• Development of a disease model integrating genetic predisposition, immune response to antigens, and subsequent neuro-intestinal alterations.
• Speculation on future diagnostic and therapeutic strategies based on objective assessments.

Main Results:

• A proposed disease model suggests antigen exposure can trigger immune activation, low-grade inflammation, and neuronal dysfunction in genetically susceptible individuals.
• Immune activation may explain gender predominance and symptom variability in functional gastrointestinal disorders.
• The model accounts for intestinal and extraintestinal symptoms, food triggers, and comorbidity with GERD.

Conclusions:

• The traditional view of functional gastrointestinal disorders may need revision to include immune-mediated pathology.
• Future management may shift towards objective, pathology-based subtyping for personalized, targeted interventions.
• Identifying causal pathways, including immune activation and specific antigens, is crucial for developing curative treatments.