Endotoxins and Non-Alcoholic Fatty Liver Disease

作者：Takaomi Kessoku, Takashi Kobayashi, Kento Imajo, Kosuke Tanaka, Atsushi Yamamoto, Kota Takahashi, Yuki Kasai, Anna Ozaki, Michihiro Iwaki, Asako Nogami, Yasushi Honda, Yuji Ogawa, Shingo Kato, Takuma Higurashi, Kunihiro Hosono, Masato Yoneda, Takayuki Okamoto, Haruki Usuda, Koichiro Wada, Noritoshi Kobayashi, Satoru Saito, Atsushi Nakajima · 发表于：Frontiers in Endocrinology · 年份：2021 · DOI：10.3389/fendo.2021.770986 · 被引用次数：98 · 研究领域：Liver Disease Diagnosis and Treatment、Gut microbiota and health、Lipid metabolism and disorders

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 exami...