This paper proposes a microbiota–bile acid–mucus axis through which gastrointestinal physiology and disease can be understood. A two-hit instability model is introduced in which altered bile acid dynamics and impaired mucosal buffering generate persistent epithelial stress and ecological instability. The framework integrates bile acid metabolism, microbial ecology, and mucus–epithelium interactions to explain features of disorders such as Crohn’s disease and variability in treatment outcomes. Testable predictions and implications for treatment are discussed. Version 1.1: Minor revisions to clarify interpretation of epithelial metabolism-centered models and improve wording precision.
Christina Totman (Mon,) studied this question.