Nonalcoholic fatty liver disease (NAFLD) refers to a clinicopathological syndrome characterized by bullous hepatic steatosis caused by alcohol and other definite liver injury factors. According to the degree of hepatic steatosis, inflammation, and fibrosis, NAFLD can be divided into simple fatty liver and steatohepatitis, the latter can progress to more severe fatty liver fibrosis, cirrhosis, and even cancer. NAFLD is asymptomatic in the early stages of disease development, thus delaying the diagnosis of early clinical disease. Even during the progression of the disease, there is a lack of noninvasive diagnostic tools for reliable diagnosis and staging. Previous research reports have demonstrated that NAFLD patients have significantly elevated levels of endotoxin in the blood and liver compared to normal. Therefore, the concentration of endotoxin in the blood is used as a potential biomarker of NAFLD to judge the occurrence of the disease. NAFLD has reversible changes in the early stage, so an endotoxin diagnostic system is indispensable for disease monitoring at this stage.
Figure 1. Schematic diagram of the gut-liver axis in non-alcoholic fatty liver disease/non-alcohol fatty liver disease. (Kobayashi T, et al., 2022)
Endotoxins from Gram-negative bacilli have been implicated as a contributing factor to NAFLD, the most common chronic liver disease with high prevalence. Studies have confirmed that a leaky gut caused by impaired intestinal barrier function can lead to intestinal bacterial imbalance and promote endotoxins to enter the liver, which can cause hepatitis and liver damage. And for some patients, low doses of endotoxin can cause liver damage. Therefore, elevated endotoxin levels in the blood can promote the progression of NAFLD. The medical diagnosis of NAFLD often utilizes methods such as B-ultrasound, CT, and liver puncture liver biopsy. However, there is a lack of non-invasive tools for the diagnosis of NAFLD, both in the early stages of NAFLD and during disease progression. Elevated local and systemic endotoxin levels have some pro-inflammatory and pro-fibrotic effects, thereby driving the progression of liver disease. The results of the study have confirmed that blood endotoxin levels can be used as a new type of relevant diagnostic biomarker for NAFLD compared with traditional diagnostic methods. Endotoxin levels can be used both for disease detection and staging during disease progression and as an index of intestinal permeability in NAFLD. Most researchers directly evaluate the level of endotoxin in blood by using limulus amebocyte lysate (LAL) to measure endotoxin, and endotoxin plays an important role as a key indicator in clinical application.
The pathogenesis and progression of NAFLD are closely related to endotoxin, and the level of endotoxin in the blood of NAFLD patients is found to be significantly higher than normal, which indicates that blood endotoxin level can be used as a potential biomarker of NAFLD. As a fast, efficient, and accurate method, endotoxin detection can participate in the diagnosis of NAFLD in future clinical applications and help medical staff monitor the development of the disease more conveniently.
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