Circulating microbiota-derived metabolites: a "liquid biopsy?

Area of Science:

• Hepatology
• Gastroenterology
• Metabolomics

Background:

• Non-alcoholic fatty liver disease (NAFLD) encompasses a range of liver damage, from simple steatosis (SS) to cirrhosis.
• Distinguishing between SS and non-alcoholic steatohepatitis (NASH) clinically or via lab tests is challenging.
• Gut microbiota dysregulation is implicated in the pathogenesis of NASH.

Purpose of the Study:

• To investigate the association between microbiota-derived metabolites and the severity of NAFLD.
• To explore the potential of these metabolites as biomarkers for NASH diagnosis.

Main Methods:

• Serum analysis using liquid chromatography-mass spectrometry (LC-QqQ) to quantify metabolites like choline derivatives, betaine, ethanol, bile acids, and short-chain fatty acids.
• Gene expression analysis (RT-PCR) in liver and jejunum tissues for genes involved in lipid metabolism and inflammation (e.g., TLRs, FXR, SREBP1C, FAS).
• Study population included women with normal weight and morbid obesity, with or without NAFLD, SS, or NASH.

Main Results:

• Hepatic expression of FAS, TLR2, and TLR4 was elevated in NAFLD patients; TLR2 was also upregulated in NASH.
• Intestinal TLR9 expression was upregulated, and FXR expression was downregulated in NASH patients with morbid obesity.
• Circulating levels of TMAO, glycocholic acid, and deoxycholic acid were increased in NAFLD patients.
• Endogenous circulating ethanol levels were higher in NASH patients compared to SS patients.

Conclusions:

• The intestine plays a role in NAFLD progression.
• Specific circulating microbiota-related metabolites are linked to NAFLD severity.
• These metabolites show promise as a noninvasive "liquid biopsy" for NASH diagnosis.