Physiological mechanisms of unexplained (functional) gastrointestinal disorders

Area of Science:

• Gastroenterology and Immunology
• Microbiome Research

Background:

• Functional gastrointestinal disorders (FGIDs) are characterized by overlapping symptoms without clear pathology.
• Emerging evidence suggests sub-clinical issues like increased intestinal permeability and altered gut microbiota.

Purpose of the Study:

• To re-evaluate the 'functional' designation of FGIDs by exploring underlying homeostatic imbalances.
• To investigate the link between gastrointestinal function, immune response, and FGID mechanisms.

Main Methods:

• Literature review and synthesis of current research on FGIDs.
• Analysis of physiological, biochemical, and immunological data related to FGIDs.
• Exploration of host-microbial interactions and metabolic alterations.

Main Results:

• FGIDs represent disorders of homeostatic imbalance, not a lack of organic cause.
• These imbalances involve disruptions in host and microbial function, metabolism, and immune responses.
• Extraintestinal manifestations like fatigue and psychological comorbidities are linked to gastrointestinal disruption.

Conclusions:

• FGIDs require a paradigm shift from 'functional' to a focus on homeostatic dysregulation.
• Understanding gut-immune-microbiome interactions is key to identifying FGID mechanisms.
• Future research should focus on high-level phenotyping, sex hormones, and microbial metabolites for therapeutic targets.