Rifaximin alleviates MCD diet-induced NASH in mice by restoring the gut microbiota and intestinal barrier.

Life Sci

Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China. Electronic address:

Published: November 2024

AI Article Synopsis

  • * Researchers created a NASH model in mice using a specific diet and administered rifaximin at different times to assess its preventive and therapeutic effects.
  • * Results showed that rifaximin significantly reduced NASH symptoms by restoring gut microbiota and improving intestinal barrier function, and it affected key liver proteins, suggesting it could be a new treatment strategy for NASH.

Article Abstract

Aims: Due to the increasing global incidence rate of nonalcoholic steatohepatitis (NASH) combined with the lack of effective treatment methods for this disease, there is an urgent need to find new treatment strategies. The aim of this study was to investigate the efficacy of rifaximin in preventing and treating NASH and the related mechanism.

Materials And Methods: A NASH model was constructed by feeding male C57BL/6 mice a methionine-choline-deficient (MCD) diet for 4 weeks. Rifaximin was administered for 1 week before MCD diet feeding or during the last week of MCD diet feeding to investigate its preventive or therapeutic effects. Liver pathology, hepatic enzyme levels and metabolic indices were measured to evaluate the effects of rifaximin on NASH. Intestinal barrier integrity was measured via the Ussing chamber system and western blotting. 16S rDNA sequencing was conducted to investigate the fecal microbiota composition. Western blotting was performed to evaluate peroxisome proliferator activated receptor (PPAR)α and PPARγ protein levels.

Key Findings: Rifaximin effectively alleviated MCD diet-induced NASH. The microbiota composition in MCD diet-fed mice was significantly altered, and intestinal barrier integrity was disrupted. Dysbiosis and intestinal barrier dysfunction were reversed by rifaximin. In addition, rifaximin modulated PPARα and PPARγ expression in the liver.

Significance: Rifaximin effectively alleviated MCD diet-induced NASH by restoring the gut microbiota and reversing intestinal barrier dysfunction, suggesting that rifaximin treatment is a new approach for preventing and treating NASH.

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Source
http://dx.doi.org/10.1016/j.lfs.2024.123095DOI Listing

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