Oleanolic Acid Improves Gut Atrophy Induced by Parenteral Nutrition.
BACKGROUND
Nutrition support with parenteral nutrition (PN) is associated with gut atrophy. Prior studies have shown improvement with enteral chenodeoxycholic acid, a dual agonist for the farnesoid X receptor (FXR) and bile acid receptor TGR5. We hypothesized that gut growth is induced by TGR5 activation, and gut atrophy during PN administration could be prevented with the TGR5-specific agonist oleanolic acid (OA).


METHODS
Neonatal pigs were implanted with duodenal and jugular vein catheters. Animals were provided equi-nutritious PN or enteral swine milk. A PN subgroup received enteral OA at 50 mg/kg/d.


RESULTS
PN caused marked gut atrophy compared with enterally fed (EN) control animals. OA treatment led to preservation of gut mass demonstrated grossly and histologically. The mean ± SD gut weight as a percentage of body weight was 4.30 ± 0.26 for EN, 1.92 ± 0.06 for PN (P < .05, EN vs PN), and 3.39 ± 0.79 for PN+OA (P < .05, PN+OA vs PN). Mean ± SD gut density (g/cm) was 0.31 ± 0.03 for EN, 0.18 ± 0.03 for PN (P < .05 EN vs PN), and 0.27 ± 0.01 for PN+OA (P < .05 PN+OA vs PN). Histologically, a markedly decreased villous to crypt ratio was noted with PN, and OA significantly prevented this decrease. The mean ± SD v/c ratio was 3.51 ± 0.59 for EN, 1.69 ± 0.10 for PN (P < .05, EN vs PN), and 2.90 ± 0.23 for PN+OA (P < .05, PN+OA vs PN). Gut TGR5 messenger RNA expression was significantly elevated with OA treatment compared with both PN and EN.


CONCLUSIONS
The bile acid-activated G protein-coupled receptor TGR5 agonist OA prevented gut atrophy associated with PN.
Department of Pediatrics, St Louis University School of Medicine, Cardinal Glennon Children's Medical Center, St Louis, Missouri ajain3@slu.edu.
Ajay Kumar
AK
Jain
Department of Pediatrics, St Louis University School of Medicine, Cardinal Glennon Children's Medical Center, St Louis, Missouri.
Joy X
JX
Wen
Department of Pediatrics, St Louis University School of Medicine, Cardinal Glennon Children's Medical Center, St Louis, Missouri.
Keith S
KS
Blomenkamp
Department of Pediatrics, St Louis University School of Medicine, Cardinal Glennon Children's Medical Center, St Louis, Missouri.
Sumit
S
Arora
Department of Pediatrics, St Louis University School of Medicine, Cardinal Glennon Children's Medical Center, St Louis, Missouri.
Timothy A
TA
Blaufuss
Department of Pediatrics, St Louis University School of Medicine, Cardinal Glennon Children's Medical Center, St Louis, Missouri.
Jonathan
J
Rodrigues
Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, St Louis, Missouri.
John P
JP
Long
Department of Internal Medicine, St Louis University School of Medicine, St Louis, Missouri.
Brent A
BA
Neuschwander-Tetri
Department of Pediatrics, St Louis University School of Medicine, Cardinal Glennon Children's Medical Center, St Louis, Missouri.
Jeffery H
JH
Teckman
D000818:Animals; D000831:Animals, Newborn; D001284:Atrophy; D004195:Disease Models, Animal; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000473:pathology*; D009828:Oleanolic Acid / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010288:Parenteral Nutrition / Q000009:adverse effects*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D013552:Swine
D043562:Receptors, G-Protein-Coupled; D009828:Oleanolic Acid
gastroenterology; gut atrophy; neonates; oleanolic acid; parenteral nutrition; pediatrics