2. Academic Validation
  3. Obeticholic acid ameliorates severity of Clostridioides difficile infection in high fat diet-induced obese mice

Obeticholic acid ameliorates severity of Clostridioides difficile infection in high fat diet-induced obese mice

  • Mucosal Immunol. 2021 Mar;14(2):500-510. doi: 10.1038/s41385-020-00338-7.
Shinsmon Jose 1,  Anindita Mukherjee 1,  Olivia Horrigan 1,  Kenneth D R Setchell 2 3,  Wujuan Zhang 2,  Maria E Moreno-Fernandez 3 4,  Heidi Andersen 5,  Divya Sharma 6,  David B Haslam 5,  Senad Divanovic 3 4 7,  Rajat Madan 8 9 10
Affiliations

Affiliations

  • 1 Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.
  • 2 Department of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
  • 3 Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.
  • 4 Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
  • 5 Department of Pediatric Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
  • 6 Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.
  • 7 Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
  • 8 Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA. rajat.madan@uc.edu.
  • 9 Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA. rajat.madan@uc.edu.
  • 10 Veterans Affairs Medical Center, Cincinnati, OH, 45220, USA. rajat.madan@uc.edu.
PMID: 32811993 DOI: 10.1038/s41385-020-00338-7
Abstract

Severe Clostridiodes difficile Infection (CDI) is life-threatening and responds poorly to treatment. Obesity is associated with development of severe CDI. Therefore, to define the mechanisms that exacerbate disease severity, we examined CDI pathogenesis in high-fat diet (HFD)-fed obese mice. Compared to control mice, HFD-fed mice failed to clear C. difficile bacteria which resulted in protracted diarrhea, weight loss and colonic damage. After Infection, HFD-induced obese mice had an intestinal bile acid (BA) pool that was dominated by primary BAs which are known promoters of C. difficile spore germination, and lacked secondary BAs that inhibit C. difficile growth. Concurrently, synthesis of primary BAs from liver was significantly increased in C. difficile-infected HFD-fed mice. A key pathway that regulates hepatic BA synthesis is via feedback inhibition from intestinal Farnesoid X receptors (FXRs). Our data reveal that the proportion of FXR Agonist BAs to FXR antagonist BAs in the intestinal lumen was significantly reduced in HFD-fed mice after CDI. Treatment of HFD-fed mice with an FXR Agonist Obeticholic acid, resulted in decreased primary BA synthesis, fewer C. difficile bacteria and better CDI outcomes. Thus, OCA treatment holds promise as a therapy for severe CDI.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z