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Ursodeoxycholic acid and its taurine/glycine conjugated species reduce colitogenic dysbiosis and equally suppress experimental colitis in mice

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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.
Keywords
bile acids, colitis, dysbiosis, BUTYRATE-PRODUCING BACTERIA, INFLAMMATORY BOWEL DISEASES, 16S RIBOSOMAL-RNA, BILE-ACID, GUT MICROBIOTA, AKKERMANSIA-MUCINIPHILA, INTESTINAL MICROBIOTA, ULCERATIVE-COLITIS, CROHNS-DISEASE, IN-VITRO

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Chicago
Van den Bossche, Lien, PIETER HINDRYCKX, Lindsey Devisscher, Sarah Devriese, Sophie Van Welden, Tom Holvoet, Ramiro Vilchez Vargas, et al. 2017. “Ursodeoxycholic Acid and Its Taurine/glycine Conjugated Species Reduce Colitogenic Dysbiosis and Equally Suppress Experimental Colitis in Mice.” Applied and Environmental Microbiology 83 (7).
APA
Van den Bossche, L., HINDRYCKX, P., Devisscher, L., Devriese, S., Van Welden, S., Holvoet, T., Vilchez Vargas, R., et al. (2017). Ursodeoxycholic acid and its taurine/glycine conjugated species reduce colitogenic dysbiosis and equally suppress experimental colitis in mice. APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 83(7).
Vancouver
1.
Van den Bossche L, HINDRYCKX P, Devisscher L, Devriese S, Van Welden S, Holvoet T, et al. Ursodeoxycholic acid and its taurine/glycine conjugated species reduce colitogenic dysbiosis and equally suppress experimental colitis in mice. APPLIED AND ENVIRONMENTAL MICROBIOLOGY. 2017;83(7).
MLA
Van den Bossche, Lien, PIETER HINDRYCKX, Lindsey Devisscher, et al. “Ursodeoxycholic Acid and Its Taurine/glycine Conjugated Species Reduce Colitogenic Dysbiosis and Equally Suppress Experimental Colitis in Mice.” APPLIED AND ENVIRONMENTAL MICROBIOLOGY 83.7 (2017): n. pag. Print.
@article{8502459,
  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.},
  articleno    = {e02766},
  author       = {Van den Bossche, Lien and Hindryckx, Pieter and Devisscher, Lindsey and Devriese, Sarah and Van Welden, Sophie and Holvoet, Tom and Vilchez Vargas, Ramiro and Vital, Marius and Pieper, Dietmar H and Vandenbussche, Julie and Vanhaecke, Lynn and Van de Wiele, Tom and De Vos, Martine and Laukens, Debby},
  issn         = {0099-2240},
  journal      = {APPLIED AND ENVIRONMENTAL MICROBIOLOGY},
  keyword      = {bile acids,colitis,dysbiosis,BUTYRATE-PRODUCING BACTERIA,INFLAMMATORY BOWEL DISEASES,16S RIBOSOMAL-RNA,BILE-ACID,GUT MICROBIOTA,AKKERMANSIA-MUCINIPHILA,INTESTINAL MICROBIOTA,ULCERATIVE-COLITIS,CROHNS-DISEASE,IN-VITRO},
  language     = {eng},
  number       = {7},
  pages        = {13},
  title        = {Ursodeoxycholic acid and its taurine/glycine conjugated species reduce colitogenic dysbiosis and equally suppress experimental colitis in mice},
  url          = {http://dx.doi.org/10.1128/AEM.02766-16},
  volume       = {83},
  year         = {2017},
}

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