Rifaximin and lubiprostone mitigate liver fibrosis development by repairing gut barrier function in diet–induced rat steatohepatitis

• Material Type: 博士論文
• Title: Rifaximin and lubiprostone mitigate liver fibrosis development by repairing gut barrier function in diet–induced rat steatohepatitis
• Author/Editor: Enomoto, Masahide; Kaji, Kosuke; Nishimura, Norihisa; Fujimoto, Yuki; Murata, Koji; Takeda, Soichi; Tsuji, Yuki; Fujinaga, Yukihisa; Tanaka, Hiroaki; Kawaratani, Hideto; Namisaki, Tadashi; Akahane, Takemi; Yoshiji, Hitoshi
• Author Heading: Enomoto, Masahide; Kaji, Kosuke; Nishimura, Norihisa; Fujimoto, Yuki; Murata, Koji; Takeda, Soichi; Tsuji, Yuki; Fujinaga, Yukihisa; Tanaka, Hiroaki; Kawaratani, Hideto; Namisaki, Tadashi; Akahane, Takemi; Yoshiji, Hitoshi
• Publication, Distribution, etc.: Elsevier
• Publication Date: 2022-10
• Publication Date (W3CDTF): 2022-10
• Alternative Title: リファキシミンとルビプロストンの併用は脂肪性肝炎ラットの腸管バリア機能を修復し肝線維化を抑制する
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2023-03-15
• Date Granted (W3CDTF): 2023-03-15
• Dissertation Number: 甲第860号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Gut-liver axis; Lipopolysaccharide; Microbiome; Non-alcoholic steatohepatitis
• Target Audience: 一般
• Note (General): type:Thesis; 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, molec- ular, 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 perme- ability 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.; 博士（医学）・甲第860号・令和5年3月15日; identifier:Digestive and liver disease Vol.54 No.10 p.1392-1402 (2022 Oct); identifier:15908658; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4091; identifier:Digestive and liver Disease, 54(10): 1392-1402
• Persistent ID (NDL): info:ndljp/pid/13122557; https://dl.ndl.go.jp/pid/13122557
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• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2023-12-15T22:13:24+09:00
• Format (IMT): application/pdf
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• Periodical Title (URI): http://hdl.handle.net/10564/4091
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