Does intestinal mucosal inflammation impair bile acid handling and fat absorption?

Intestinal mucosal inflammation directly impairs the gut's ability to process dietary fats by disrupting the delicate enterohepatic circulation of bile acids. This disruption forms a pathological cycle that exacerbates both malabsorption and tissue injury.

Mechanistic cascade of bile acid disruption

• Transporter downregulation: Pro-inflammatory cytokines, specifically TNF-alpha and IL-1beta, actively suppress the expression of the apical sodium-dependent bile acid transporter (ASBT/SLC10A2) in the terminal ileum, halting normal bile acid reabsorption.
• Receptor and microbial impairment: Inflammation concurrently dampens farnesoid X receptor (FXR) signaling and alters the gut microbiota. This shift reduces the abundance of bacteria expressing bile salt hydrolase (BSH), which is essential for normal bile acid deconjugation.

Impact on lipid absorption and inflammatory feedback

• Impaired fat handling: As ASBT downregulates and BSH activity shifts, the enterohepatic pool is depleted. When luminal bile acid levels drop below the critical micellar concentration, micellar solubilization of dietary lipids fails, leading to clinical fat malabsorption and increased fecal fat excretion.
• Pro-inflammatory feedback loop: This disruption extends beyond digestion; reduced activation of bile acid receptors FXR and TGR5 removes a key anti-inflammatory brake, allowing unchecked pro-inflammatory cytokine production to further drive mucosal inflammation.

Bottom line

• Mucosal inflammation impairs dietary fat absorption by downregulating key transport proteins like ASBT, disrupting regulatory FXR/TGR5 signaling, and altering microbial deconjugation, which collectively creates a self-perpetuating cycle of inflammation and lipid malabsorption.