No Gut No Gain! Enteral Bile Acid Treatment Preserves Gut Growth but Not Parenteral Nutrition-Associated Liver Injury in a Novel Extensive Short Bowel Animal Model

Autor: Amber Price, Thomas L Ratchford, Chandrashekhara Manithody, Matthew Westrich, Miguel A. Guzman, Nicole Heafner, Niraja Korremla, William Phillips, Shruthika Pochampally, Keith Blomenkamp, Gustavo A. Villalona, Jose Greenspon, Ajay Jain, Vindhya Kakarla, Saurabh Saxena
Rok vydání: 2017
Předmět:
0301 basic medicine
Short Bowel Syndrome
medicine.medical_specialty
Parenteral Nutrition
medicine.drug_class
Swine
Medicine (miscellaneous)
Receptors
Cytoplasmic and Nuclear
Chenodeoxycholic Acid
Enteral administration
Polymerase Chain Reaction
Article
Bile Acids and Salts
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cholestasis
Internal medicine
Chenodeoxycholic acid
Intestine
Small
medicine
Animals
Receptor
Fibroblast Growth Factor
Type 4
Cholesterol 7-alpha-Hydroxylase
Nutrition and Dietetics
Bile acid
business.industry
Liver Diseases
FGF19
Short bowel syndrome
medicine.disease
Fibroblast Growth Factors
Gastrointestinal Tract
Disease Models
Animal
030104 developmental biology
Endocrinology
Parenteral nutrition
chemistry
Liver
030211 gastroenterology & hepatology
Farnesoid X receptor
Parenteral Nutrition
Total
business
Zdroj: JPEN. Journal of parenteral and enteral nutrition. 42(8)
ISSN: 1941-2444
Popis: BACKGROUND: Parenteral nutrition (PN) provides nutrition intravenously; however, this life-saving therapy is associated with significant liver disease. Recent evidence indicates improvement in PN-associated injury in animals with intact gut treated with enteral bile acid (BA), chenodeoxycholic acid (CDCA), and a gut farnesoid X receptor (FXR) agonist, which drives the gut–liver cross talk (GLCT). We hypothesized that similar improvement could be translated in animals with short bowel syndrome (SBS). METHODS: Using piglets, we developed a novel 90% gut-resected SBS model. Fifteen SBS piglets receiving PN were given CDCA or control (vehicle control) for 2 weeks. Tissue and serum were analyzed posteuthanasia. RESULTS: CDCA increased gut FXR (quantitative polymerase chain reaction; P = .008), but not downstream FXR targets. No difference in gut fibroblast growth factor 19 (FGF19; P = .28) or hepatic FXR (P = .75), FGF19 (P = .86), FGFR4 (P = .53), or Cholesterol 7 α-hydroxylase (P = .61) was noted. PN resulted in cholestasis; however, no improvement was noted with CDCA. Hepatic fibrosis or immunostaining for Ki67, CD3, or Cytokeratin 7 was not different with CDCA. PN resulted in gut atrophy. CDCA preserved (P = .04 vs control) gut mass and villous/crypt ratio. The median (interquartile range) for gut mass for control was 0.28 (0.17–0.34) and for CDCA was 0.33 (0.26–0.46). CONCLUSIONS: We note that, unlike in animals with intact gut, in an SBS animal model there is inadequate CDCA-induced activation of gut-derived signaling to cause liver improvement. Thus, it appears that activation of GLCT is critically dependent on the presence of adequate gut. This is clinically relevant because it suggests that BA therapy may not be as effective for patients with SBS.
Databáze: OpenAIRE
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