Bile acid detergency: permeability, inflammation, and effects of sulfation

Abstract

Bile acids are amphipathic, detergent molecules. The detergent effects of di-α-hydroxy-bile acids are relevant to several colonic diseases. The aims were to review the concentrations of bile acids reaching the human colon in health and disease, the molecular structure of bile acids that determine detergent functions and the relationship to human diseases (neuroendocrine tumors, microscopic colitis, active celiac disease, and ulcerative colitis, Crohn’s disease and ileal resection), the relationship to bacterial uptake into the mucosa, mucin depletion, and epithelial damage, the role of bile acids in mucosal inflammation and microscopic colitis, and the role of sulfation of bile salts in detoxification or prevention of the detergent effects of bile acids. The concentrations of bile acids reaching the human colon range from 2 to 10 mM; di-α-hydroxy bile acids are the only bile acids with detergent effects that include mucin depletion, mucosal damage, bacterial uptake, and microscopic inflammation that may be manifest in diseases associated with no overt inflammation of the mucosa, such as bile acid diarrhea, ileal diseases such as neuroendocrine tumors, ileal resection, and nonalcoholic steatohepatitis. Sulfation inactivates colonic secretion due to primary bile acids, but it may render secondary bile acids proinflammatory in the colon. Other evidence in preclinical models of inflammatory bowel disease (IBD) suggests reduced sulfation causes barrier dysfunction, inflammation, or carcinogenesis. These advances emphasize relevance and opportunities afforded by greater understanding of the chemistry and metabolism of bile acids, which stands to be further enhanced by research into the metabolic interactions of microbiota with bile acids.