The Role of Leaky Gut in Nonalcoholic Fatty Liver Disease: A Novel Therapeutic Target

International Journal of Molecular Sciences

Kento Imajo¹  Kosuke Tanaka¹  Kota Takahashi¹  Michihiro Iwaki¹  Takuma Higurashi¹  Takashi Kobayashi¹  Kunihiro Hosono¹  Anna Ozaki¹  Satoru Saito¹  Shingo Kato¹  Masato Yoneda¹  Atsushi Nakajima¹  Atsushi Yamamoto¹  Yuji Ogawa¹  Asako Nogami¹  Yuki Kasai¹  Yasushi Honda¹  Takaomi Kessoku¹  Koichiro Wada²  Haruki Usuda² 

[1] Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan;Department of Pharmacology, Shimane University Faculty of Medicine, 89-1 Enyacho, Izumo, Shimane 693-8501, Japan;

关键词: leaky gut;    gut permeability;    nonalcoholic fatty liver disease;    nonalcoholic steatohepatitis;    endotoxin;   

DOI  :  10.3390/ijms22158161

来源: DOAJ

【 摘 要 】

The liver directly accepts blood from the gut and is, therefore, exposed to intestinal bacteria. Recent studies have demonstrated a relationship between gut bacteria and nonalcoholic fatty liver disease (NAFLD). Approximately 10–20% of NAFLD patients develop nonalcoholic steatohepatitis (NASH), and endotoxins produced by Gram-negative bacilli may be involved in NAFLD pathogenesis. NAFLD hyperendotoxicemia has intestinal and hepatic factors. The intestinal factors include impaired intestinal barrier function (leaky gut syndrome) and dysbiosis due to increased abundance of ethanol-producing bacteria, which can change endogenous alcohol concentrations. The hepatic factors include hyperleptinemia, which is associated with an excessive response to endotoxins, leading to intrahepatic inflammation and fibrosis. Clinically, the relationship between gut bacteria and NAFLD has been targeted in some randomized controlled trials of probiotics and other agents, but the results have been inconsistent. A recent randomized, placebo-controlled study explored the utility of lubiprostone, a treatment for constipation, in restoring intestinal barrier function and improving the outcomes of NAFLD patients, marking a new phase in the development of novel therapies targeting the intestinal barrier. This review summarizes recent data from studies in animal models and randomized clinical trials on the role of the gut–liver axis in NAFLD pathogenesis and progression.

【 授权许可】

Unknown