Small intestinal bacteria accelerate aspirin-induced small intestinal injuries

Area of Science:

• Gastroenterology
• Pharmacology
• Microbiology

Background:

• Enteric-coated low-dose aspirin (LDA) can cause small intestinal mucosal injuries.
• The exact mechanisms behind these injuries remain unclear.
• Aspirin (acetylsalicylic acid, ASA) is a precursor to salicylic acid (SA), a known cytotoxic agent.

Purpose of the Study:

• To investigate the mechanism of ASA deacetylation to SA in the small intestine.
• To determine if SA is the direct cause of LDA-induced mucosal injuries.

Main Methods:

• ASA deacetylation and cell damage were assessed in various conditions, including different pH buffers, pancreatic enzymes, and IEC-6 cell homogenates.
• Caecum bacterial suspension (CBS) was used to study ASA deacetylation.
• ASA and CBS were co-injected into murine duodenum to evaluate in vivo small intestinal damage.

Main Results:

• ASA deacetylation to SA was significantly promoted by CBS, indicating bacterial esterase involvement.
• In vitro, ASA was minimally deacetylated by buffers, pancreatic enzymes, or IEC-6 cell homogenates.
• Co-injection of ASA and CBS into mice led to severe small intestinal injuries, unlike ASA alone.

Conclusions:

• Small intestinal mucosal injuries from enteric-coated LDA are primarily caused by the direct cytotoxicity of SA.
• SA is formed through the deacetylation of ASA by enterobacterial esterases in the small intestine.