Dose-dependent antiinflammatory effect of ursodeoxycholic acid in experimental colitis

Martínez-Moya, Patricia; Romero‐Calvo, Isabel; Requena, Pilar; Hernández‐Chirlaque, Cristina; Aranda, Carlos J.; González, Raquel Luengo; Zarzuelo, Antonio; Suárez, Marı́a Dolores; Martínez‐Augustin, Olga; Marin, J. J. G.

doi:10.1016/j.intimp.2012.11.017

Cited by 85 publications

(68 citation statements)

References 20 publications

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“…Previous studies have reported the therapeutic potential of the hydrophilic bile acids UDCA and TUDCA in experimental colitis (11,15,16), albeit without comparing their respective effectiveness. In the present study, we showed that daily administration of UDCA and its taurine-and glycine-coupled conjugates equally attenuated body weight loss, disease activity, and colonic shortening caused by DSS.…”

Section: Discussionmentioning

confidence: 99%

“…Because secondary bile acids exhibit immunomodulatory functions (7)(8)(9)(10), increasing secondary bile acid levels in the intestinal lumen could be an efficient therapeutic approach for IBD. In line with this hypothesis, the administration of the secondary hydrophilic bile acid ursodeoxycholic acid (UDCA) ameliorates experimental colitis, but the exact mechanism protecting from colitogenesis is not fully understood (11).…”

mentioning

confidence: 99%

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

Bossche

Hindryckx

Devisscher

et al. 2017

Appl Environ Microbiol

112

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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.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Bossche

Hindryckx

Devisscher

et al. 2017

Appl Environ Microbiol

112

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“…Those of group III were treated daily with UDCA suspended in normal saline (50 mg/kg, i.p. ; Minapharm Pharmaceutical, Cairo, Egypt) [29] for 3 weeks, 1 h before rotenone on the days of the insecticide injection. Twenty-four hours after the last injection of rotenone, all rats were screened for motor impairment using the open field test.…”

Section: Experimental Designmentioning

confidence: 99%

Ursodeoxycholic Acid Ameliorates Apoptotic Cascade in the Rotenone Model of Parkinson’s Disease: Modulation of Mitochondrial Perturbations

2014

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The recent emergence of ursodeoxycholic acid (UDCA) as a contender in modifying neurotoxicity in human dopaminergic cells as well as its recognized anti-apoptotic and anti-inflammatory potentials in various hepatic pathologies raised impetus in investigating its anti-parkinsonian effect in rat rotenone model. UDCA prominently improved motor performance in the open field test and halted the decline in the striatal dopamine content. Meanwhile, it improved mitochondrial function as verified by elevation of ATP associated with preservation of mitochondrial integrity as portrayed in the electron microscope examination. In addition, through its anti-inflammatory potential, UDCA reduced the rotenone-induced nuclear factor-κB expression and tumor necrosis factor alpha level. Furthermore, UDCA amended alterations in Bax and Bcl-2 and reduced the activities of caspase-8, caspase-9, and caspase-3, indicating that it suppressed rotenone-induced apoptosis via modulating both intrinsic and extrinsic pathways. In conclusion, UDCA can be introduced as a novel approach for the management of Parkinson's disease via anti-apoptotic and anti-inflammatory mechanisms. These effects are probably linked to dopamine synthesis and mitochondrial regulation.

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“…The bile acid, ursodeoxycholic acid (UDCA) has shown great potential in diabetes treatment through its effects on inflammation and cell viability. 14,47 Our recent studies focused on refining and optimising new cell-microencapsulation methods and also screening different polyelectrolytes at various ratios, to optimise cell viability, postmicroencapsulation. [15][16][17][18]24,31,32 Thus, this study aims to refine further the microencapsulating method focusing on optimising nozzle temperature and nozzle-gelation bath distance, to produce best capsules.…”

Section: Introductionmentioning

confidence: 99%

Biological Assessments of Encapsulated Pancreatic β-Cells: Their Potential Transplantation in Diabetes

et al. 2016

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Microencapsulation of pancreatic islets has been considered as a promising method for cell transplantation and diabetes treatment. However, in vivo trials to date have been hampered by fibrotic overgrowth and very limited to no success, long-term. Future success requires suitable microencapsulating method and possibly a simplified and suitable formulation which will produce a microcapsule that provides an immunobarrier, maintain full b-cell functionality whilst also reducing the inflammatory processes that induce fibrosis. In multiple studies, we screened various formulations and microencapsulating methods, and obtained promising results using bile acid-based microcapsules containing b-cells, in terms of cell functions and insulin release. Thus, this study aimed to refine further the microencapsulating method using a simple alginate-poly-L-ornithine formulation and test the effect of adding a promising bile acid, ursodeoxycholic acid (UDCA), on cell functions. Using Bu¨chi concentric nozzle, viable NIT-1 cells were microencapsulated using alginatepoly-L-ornithine, with or without UDCA at a ratio of 1:1.2 or 1:1.2:4. Screening for nozzle temperature and nozzlegelation bath distance was carried out to form best microcapsules. Microcapsules were cultured for 48 h and examined for size and surface morphology, chemical profiling and bcell viability. Culture supernatants were examined for insulin and inflammatory cytokines. When using 30°C nozzletemperature and 5 cm nozzle-gelation bath distance, in the presence of the bile acid, cell mitochondrial activities and insulin production were optimised. Under deployed microencapsulating method with nozzle-temperature of 30°C and nozzle-gelation bath distance of 5 cm, the incorporation of the bile acid into the microcapsules resulted in enhanced bcell survival, function and improved overall biocompatibility supporting potential applications in transplantation.

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Dose-dependent antiinflammatory effect of ursodeoxycholic acid in experimental colitis

Cited by 85 publications

References 20 publications

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

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

Ursodeoxycholic Acid Ameliorates Apoptotic Cascade in the Rotenone Model of Parkinson’s Disease: Modulation of Mitochondrial Perturbations

Biological Assessments of Encapsulated Pancreatic β-Cells: Their Potential Transplantation in Diabetes

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