Oleanolic Acid Improves Gut Atrophy Induced by Parenteral Nutrition

Area of Science:

• Gastroenterology
• Pharmacology
• Cell Biology

Background:

• Parenteral nutrition (PN) is linked to gut atrophy, impacting intestinal health.
• Chenodeoxycholic acid, a dual farnesoid X receptor (FXR) and TGR5 agonist, has previously shown benefits.
• This study investigates the potential of TGR5 activation to counteract PN-induced gut atrophy.

Purpose of the Study:

• To determine if TGR5 receptor activation by oleanolic acid (OA) can prevent gut atrophy during PN.
• To evaluate the effects of OA on gut mass, histology, and TGR5 expression in a neonatal pig model.

Main Methods:

• Neonatal pigs received either PN or enteral nutrition (swine milk).
• A subset of PN-fed pigs received enteral oleanolic acid (OA) at 50 mg/kg/d.
• Gut weight, density, villous to crypt ratio, and TGR5 mRNA expression were analyzed.

Main Results:

• PN significantly reduced gut weight and density, causing atrophy compared to enteral feeding.
• OA treatment preserved gut mass and density, significantly mitigating atrophy.
• OA prevented the decrease in villous to crypt ratio and increased gut TGR5 mRNA expression.

Conclusions:

• Oleanolic acid (OA), a TGR5 agonist, effectively prevented gut atrophy associated with parenteral nutrition.
• TGR5 activation is a promising therapeutic target for preventing gut atrophy during PN.