Endotoxins and Non-Alcoholic Fatty Liver Disease.
NAFLD
endotoxin
intestinal permeability
leaky gut
small intestinal bacterial overgrowth
Journal
Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782
Informations de publication
Date de publication:
2021
2021
Historique:
received:
05
09
2021
accepted:
18
10
2021
entrez:
15
11
2021
pubmed:
16
11
2021
medline:
17
2
2022
Statut:
epublish
Résumé
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. It occurs with a prevalence of up to 25%, of which 10-20% cases progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. The histopathology of NASH is characterized by neutrophilic infiltration, and endotoxins from gram-negative rods have been postulated as a contributing factor. Elevations in endotoxin levels in the blood can be classified as intestinal and hepatic factors. In recent years, leaky gut syndrome, which is characterized by impaired intestinal barrier function, has become a significant issue. A leaky gut may prompt intestinal bacteria dysbiosis and increase the amount of endotoxin that enters the liver from the portal vein. These contribute to persistent chronic inflammation and progressive liver damage. In addition, hepatic factors suggest that liver damage can be induced by low-dose endotoxins, which does not occur in healthy individuals. In particular, increased expression of CD14, an endotoxin co-receptor in the liver, may result in leptin-induced endotoxin hyper-responsiveness in obese individuals. Thus, elevated blood endotoxin levels contribute to the progression of NASH. The current therapeutic targets for NASH treat steatosis and liver inflammation and fibrosis. While many clinical trials are underway, no studies have been performed on therapeutic agents that target the intestinal barrier. Recently, a randomized placebo-controlled trial examined the role of the intestinal barrier in patients with NAFLD. To our knowledge, this study was the first of its kind and study suggested that the intestinal barrier may be a novel target in the future treatment of NAFLD.
Identifiants
pubmed: 34777261
doi: 10.3389/fendo.2021.770986
pmc: PMC8586459
doi:
Substances chimiques
Endotoxins
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
770986Informations de copyright
Copyright © 2021 Kessoku, Kobayashi, Imajo, Tanaka, Yamamoto, Takahashi, Kasai, Ozaki, Iwaki, Nogami, Honda, Ogawa, Kato, Higurashi, Hosono, Yoneda, Okamoto, Usuda, Wada, Kobayashi, Saito and Nakajima.
Déclaration de conflit d'intérêts
ANa receives grants and research support from Gilead, Mylan EPD, EA Pharma, Kowa, Taisho, and Biofermin. ANa is also a consultant for Gilead, Boehringer Ingelheim, Bristol Myers Squibb, Kowa, Astellas, EA Pharma, and Mylan EPD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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