Can gut microbial bile acid deconjugation impair fat digestion?

The gastrointestinal microbiota plays a primary role in regulating host lipid metabolism through the enzymatic modification of bile acids.

Biochemical mechanisms of deconjugation

• Enzymatic cleavage: Gut microbes across major phyla (such as Lactobacillus, Bifidobacterium, and Bacteroides) express bile salt hydrolases (BSHs) and metalloBSHs that cleave the C-24 amide bond of glycine- and taurine-conjugated bile acids, yielding free unconjugated bile acids.
• Premature absorption: In conditions like small intestinal bacterial overgrowth (SIBO)—which is increasingly common in older adults due to age-related changes in gut motility—proximal bacterial colonization leads to premature deconjugation.
• Mucosal toxicity: The resulting free bile acids are highly lipophilic and undergo rapid, passive reabsorption in the jejunum. Furthermore, these unconjugated bile acids exert direct toxic effects on the intestinal epithelial barrier, promoting mucosal inflammation and increased permeability.

Impact on lipid digestion

• Micellar disruption: Premature absorption depletes the luminal conjugated bile acid pool, preventing it from reaching the critical micellar concentration required for lipid solubilization.
• Impaired digestion: Without sufficient conjugated bile salts to act as detergents, dietary lipids cannot be effectively emulsified into mixed micelles. This impairs downstream enzymatic triglyceride breakdown by pancreatic lipases, leading to fat malabsorption, fat-soluble vitamin deficiencies, and clinical steatorrhea.

Bottom line

• Bottom line: Excessive or misplaced microbial deconjugation of bile acids in the proximal small intestine depletes the conjugated bile acid pool, compromising micelle formation and lipid digestion while promoting mucosal toxicity and fat malabsorption.