Ursodeoxycholic Acid and Its Taurine- or Glycine-Conjugated Species Reduce Colitogenic Dysbiosis and Equally Suppress Experimental Colitis in Mice.

Abstract

The promising results seen in studies of secondary bile acids in experimental colitis suggest that they may represent an attractive and safe class of drugs for the treatment of inflammatory bowel diseases (IBD). However, the exact mechanism by which bile acid therapy confers protection from colitogenesis is currently unknown. Since the gut microbiota plays a crucial role in the pathogenesis of IBD, and exogenous bile acid administration may affect the community structure of the microbiota, we examined the impact of the secondary bile acid ursodeoxycholic acid (UDCA) and its taurine or glycine conjugates on the fecal microbial community structure during experimental colitis. Daily oral administration of UDCA, tauroursodeoxycholic acid (TUDCA), or glycoursodeoxycholic acid (GUDCA) equally lowered the severity of dextran sodium sulfate-induced colitis in mice, as evidenced by reduced body weight loss, colonic shortening, and expression of inflammatory cytokines. Illumina sequencing demonstrated that bile acid therapy during colitis did not restore fecal bacterial richness and diversity. However, bile acid therapy normalized the colitis-associated increased ratio of Firmicutes to Bacteroidetes Interestingly, administration of bile acids prevented the loss of Clostridium cluster XIVa and increased the abundance of Akkermansia muciniphila, bacterial species known to be particularly decreased in IBD patients. We conclude that UDCA, which is an FDA-approved drug for cholestatic liver disorders, could be an attractive treatment option to reduce dysbiosis and ameliorate inflammation in human IBD.IMPORTANCE Secondary bile acids are emerging as attractive candidates for the treatment of inflammatory bowel disease. Although bile acids may affect the intestinal microbial community structure, which significantly contributes to the course of these inflammatory disorders, the impact of bile acid therapy on the fecal microbiota during colitis has not yet been considered. Here, we studied the alterations in the fecal microbial abundance in colitic mice following the administration of secondary bile acids. Our results show that secondary bile acids reduce the severity of colitis and ameliorate colitis-associated fecal dysbiosis at the phylum level. This study indicates that secondary bile acids might act as a safe and effective drug for inflammatory bowel disease.

• Authors: Lien Van den Bossche, Pieter Hindryckx, Lindsey Devisscher, Sarah Devriese, Sophie Van Welden, Tom Holvoet, Ramiro Vilchez-Vargas, Marius Vital, Dietmar H Pieper, Julie Vanden Bussche, Lynn Vanhaecke, Tom Van de Wiele, Martine De Vos, Debby Laukens
• Journal: Applied and environmental microbiology (Appl Environ Microbiol) Vol. 83 Issue 7 (04 01 2017) ISSN: 1098-5336 [Electronic] United States
• PMID: 28115375 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 American Society for Microbiology.

Chemical References

• Taurine
• Taurochenodeoxycholic Acid
• ursodoxicoltaurine
• glycoursodeoxycholic acid
• Ursodeoxycholic Acid
• Dextran Sulfate

Topics

• Animals
• Bacteroides (drug effects)
• Colon (microbiology)
• Dextran Sulfate (administration & dosage)
• Disease Models, Animal
• Dysbiosis (drug therapy)
• Feces (microbiology)
• Firmicutes (drug effects)
• Gastrointestinal Microbiome (drug effects)
• Humans
• Inflammatory Bowel Diseases (drug therapy)
• Mice
• Taurine (chemistry)
• Taurochenodeoxycholic Acid (administration & dosage, therapeutic use)
• Ursodeoxycholic Acid (administration & dosage, analogs & derivatives, chemistry, therapeutic use)