RRC ID 70518
著者 Enomoto M, Kaji K, Nishimura N, Fujimoto Y, Murata K, Takeda S, Tsuji Y, Fujinaga Y, Takaya H, Kawaratani H, Namisaki T, Akahane T, Yoshiji H.
タイトル Rifaximin and lubiprostone mitigate liver fibrosis development by repairing gut barrier function in diet-induced rat steatohepatitis.
ジャーナル Dig Liver Dis
Abstract BACKGROUND: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.
AIMS:To explore the effects of combination with rifaximin and lubiprostone on NASH liver fibrosis through the modulation of gut barrier function.
METHODS: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.
RESULTS: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.
CONCLUSION:The combination of rifaximin and lubiprostone may provide a novel strategy for treating NASH-related fibrosis.
巻・号 54(10)
ページ 1392-1402
公開日 2022-10-1
DOI 10.1016/j.dld.2022.04.012
PII S1590-8658(22)00257-2
PMID 35514019
MeSH Acetamides Amino Acids / metabolism Amino Acids / pharmacology Animals Caco-2 Cells Chloride Channels / metabolism Chloride Channels / pharmacology Choline / metabolism Choline / pharmacology Diet Humans Lipopolysaccharides / metabolism Liver / pathology Liver Cirrhosis / complications Liver Cirrhosis / prevention & control Lubiprostone / pharmacology Neuraminidase / metabolism Neuraminidase / pharmacology Non-alcoholic Fatty Liver Disease* / drug therapy Non-alcoholic Fatty Liver Disease* / etiology Non-alcoholic Fatty Liver Disease* / metabolism Pregnane X Receptor / metabolism Rats Rats, Inbred F344 Rifaximin / pharmacology Tight Junction Proteins / metabolism Toll-Like Receptor 4 / metabolism
IF 3.57
リソース情報
ヒト・動物細胞 CACO-2(RCB0988)