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

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...

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Published in:International journal of molecular sciences 2021-07, Vol.22 (15), p.8161
Main Authors: Kessoku, Takaomi, Kobayashi, Takashi, Tanaka, Kosuke, Yamamoto, Atsushi, Takahashi, Kota, Iwaki, Michihiro, Ozaki, Anna, Kasai, Yuki, Nogami, Asako, Honda, Yasushi, Ogawa, Yuji, Kato, Shingo, Imajo, Kento, Higurashi, Takuma, Hosono, Kunihiro, Yoneda, Masato, Usuda, Haruki, Wada, Koichiro, Saito, Satoru, Nakajima, Atsushi
Format: Article
Language:English
Subjects:
Adapter proteins
Animal models
Bacilli
Bacteria
Clinical trials
Constipation
Cytokines
Diet
Digestive system
Dysbacteriosis
Endotoxins
Ethanol
Fatty liver
Fibrosis
Gram-negative bacilli
Immune system
Inflammation
Intestine
Liver
Liver diseases
Metabolic syndrome
Oxidative stress
Pathogenesis
Pathophysiology
Patients
Permeability
Placebos
Probiotics
Review
Tumor necrosis factor-TNF
Veins & arteries
Weight control
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22158161