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Rifaximin and lubiprostone mitigate liver fibrosis development by repairing gut barrier function in diet–induced rat steatohepatitis
- Source :
- Digestive and Liver Disease. 54:1392-1402
- Publication Year :
- 2022
- Publisher :
- Elsevier BV, 2022.
-
Abstract
- Although gut-derived lipopolysaccharide (LPS) affects the progression of non-alcoholic steatohepatitis (NASH) pathogenesis, few studies have focused on this relationship to develop treatments for NASH.To explore the effects of combination with rifaximin and lubiprostone on NASH liver fibrosis through the modulation of gut barrier function.To induce steatohepatitis, F344 rats were fed a choline-deficient l-amino acid-defined (CDAA) diet for 12 weeks and received oral administration of rifaximin and/or lubiprostone. Histological, molecular, and fecal microbial analyses were performed. Barrier function in Caco-2 cells were assessed by in vitro assays.Combination rifaximin/lubiprostone treatment significantly suppressed macrophage expansion, proinflammatory responses, and liver fibrosis in CDAA-fed rats by blocking hepatic translocation of LPS and activation of toll-like receptor 4 signaling. Rifaximin and lubiprostone improved intestinal permeability via restoring tight junction proteins (TJPs) with the intestinal activation of pregnane X receptor and chloride channel-2, respectively. Moreover, this combination increased the abundance of Bacteroides, Lactobacillus, and Faecalibacterium as well as decreased that of Veillonella resulting in an increase of fecal short-chain fatty acids and a decrease of intestinal sialidase activity. Both agents also directly suppressed the LPS-induced barrier dysfunction and depletion of TJPs in Caco-2 cells.The combination of rifaximin and lubiprostone may provide a novel strategy for treating NASH-related fibrosis.
- Subjects :
- Lipopolysaccharides
Liver Cirrhosis
Tight Junction Proteins
Hepatology
Pregnane X Receptor
Gastroenterology
Neuraminidase
Rats, Inbred F344
Rifaximin
Choline
Diet
Rats
Toll-Like Receptor 4
Lubiprostone
Liver
Chloride Channels
Non-alcoholic Fatty Liver Disease
Acetamides
Animals
Humans
Amino Acids
Caco-2 Cells
Subjects
Details
- ISSN :
- 15908658
- Volume :
- 54
- Database :
- OpenAIRE
- Journal :
- Digestive and Liver Disease
- Accession number :
- edsair.doi.dedup.....efcd2450d50fc4dc1a6ddf5bf7441fad