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A high-dose of ursodeoxycholic acid treatment alleviates liver inflammation by remodeling gut microbiota and bile acid profile in a mouse model of non-alcoholic steatohepatitis.
Li, Hu; Wang, Mingjie; Chen, Peizhan; Zhu, Mingyu; Chen, Li.
Afiliación
  • Li H; Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 201821, China; Department of Infectious Disease, Shanghai Jiao Tong University Affiliated Sixth People`s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200235, China.
  • Wang M; Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 201821, China.
  • Chen P; Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 201821, China.
  • Zhu M; Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 201821, China.
  • Chen L; Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 201821, China. Electronic address: drchenli@163.com.
Biomed Pharmacother ; 174: 116617, 2024 May.
Article en En | MEDLINE | ID: mdl-38643542
ABSTRACT
Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid commonly used for treating cholestatic liver disease. However, its efficacy on non-alcoholic steatohepatitis (NASH) was controversial. This study aimed to investigate the impact of a high dosage of UDCA on a mouse model of NASH. Forty 6-week-old mice were fed a high-fat high-cholesterol (HFHC) diet for 12 weeks to establish a mouse model of NASH, and then divided into four groups two groups transitioned to a normal diet, and the other two groups maintained the HFHC diet. Each group was administered a daily dosage of 300 mg/kg of UDCA or saline for a period of 8 weeks. The 16 s ribosomal RNA genes extracted from mice fecal pellets were sequenced using next-generation sequencing techniques. Serum bile acid profiles were quantified using liquid chromatography electrospray ionization tandem mass spectrometry method. The results showed that UDCA treatment ameliorated liver inflammation, without affecting liver fibrosis. UDCA treatment reduced the relative abundance of the genera Bacteroides, Parabacteroides, and Intestinimonas, whereas increased the relative abundance of the genera norank_f_Muribaculaceae and Parasutterella in the HFHC-maintaining groups. The serum levels of total bile acids and total primary bile acids increased, whereas those of endogenous primary bile acids decreased after UDCA treatment. Correlation analysis showed that primary bile acids were negatively correlated with the genera norank_f_Christensenellaceae and unclassified_f_Ruminococcaceae. In conclusion, a high dosage of UDCA can alleviate liver inflammation, probably by modifying the composition of gut microbiota and serum bile acid profiles in NASH mice.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Ácido Ursodesoxicólico / Ácidos y Sales Biliares / Modelos Animales de Enfermedad / Enfermedad del Hígado Graso no Alcohólico / Microbioma Gastrointestinal / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Biomed Pharmacother Año: 2024 Tipo del documento: Article

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Ácido Ursodesoxicólico / Ácidos y Sales Biliares / Modelos Animales de Enfermedad / Enfermedad del Hígado Graso no Alcohólico / Microbioma Gastrointestinal / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Biomed Pharmacother Año: 2024 Tipo del documento: Article