Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse...

Area of Science:

• Gastroenterology
• Hepatology
• Microbiology

Background:

• Proton pump inhibitors (PPIs) are widely prescribed globally.
• PPIs are known to modulate gut microbiota, potentially contributing to conditions like obesity.
• PPIs can induce microbiota changes independent of diet, making them a model for studying non-alcoholic fatty liver disease (NAFLD).

Purpose of the Study:

• To investigate the effects of pantoprazole, a PPI, on gut microbiota, ileum barrier integrity, and liver histology in mice.
• To explore the correlation between PPI-induced microbiota modulation and the development of liver injury, specifically microvesicular steatosis and fibrosis.
• To assess the role of Toll-like receptor 4 (TLR4) signaling in PPI-induced liver damage.

Main Methods:

• C57BL/6J mice were treated with pantoprazole for 60 days.
• Evaluated glucose and insulin tolerance, serum lipopolysaccharide (LPS) levels, and liver histology.
• Analyzed liver and intestine tissues using Western blot and qPCR; fecal microbiota were assessed via metagenomics.

Main Results:

• Pantoprazole treatment induced significant microbiota modulation and impaired ileum barrier integrity.
• Elevated circulating LPS levels and increased TLR4 and TGFβ signaling were observed.
• The study noted liver microvesicular steatosis and fibrosis, but no association with insulin resistance.

Conclusions:

• Chronic pantoprazole use alters gut microbiota and ileum barrier function.
• Increased LPS and TLR4/TGFβ signaling appear to play a role in PPI-induced liver steatosis and fibrosis.
• This PPI-induced microbiota modulation model is valuable for studying NAFLD pathogenesis.