Non-alcoholic fatty liver disease (NAFLD) has a wide spectrum that ranges from simple hepatic steatosis to non-alcoholic steatohepatitis, which can progress to fibrosis, cirrhosis and hepatocellular carcinoma.

The author of the present study evaluated the microbial metabolites, which play an active role in the development of NAFLD, such as trimethylamine, bile acids, short-chain fatty acids and ethanol. Recent technological advances in untargeted metabolomic analyses, with nuclear magnetic resonance, gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry, aid in identification of differentially regulated metabolites in patients with NAFLD. 

The severity of fibrosis in NAFLD is related to changes of metabolites in serum. Inosine and hypoxanthine, linked with nucleoside metabolism are enriched in serum samples from patients with mild or moderate NAFLD (stage 0–2 fibrosis).

It has been observed that severity of liver steatosis is associated with phenylacetic acid in humans while levels of metabolites, such as 3-(4-hydroxyphenyl) lactate, N-formylmethionine, phenyllactate, mannitol, allantoine and N-(2-furoyl) glycine, are heritable and have a shared-gene effect with hepatic steatosis and fibrosis.

Microbiota-derived metabolites in NAFLD

Choline and choline-related metabolites

Choline, an important nutrient can inluence various physiological processes in the liver such as lipid and cholesterol metabolism, signalling through lipid second messengers and enterohepatic circulation of bile acids.

Bile acids

Bile acids and their metabolites aids in maintaining hepatic glucose, cholesterol and triglyceride homeostasis. Studies showed that bile acids by altering nuclear bile acid receptor farnesoid X receptor (FXR) signalling can play a role in the development of NAFL and NASH. This FXR in turn, regulates glucose and lipid metabolism via different mechanisms, such as increasing insulin sensitivity, repressing hepatic gluconeogenic genes and increasing hepatic glycogen synthesis. 

Thus, it can be concluded that identification of microbial metabolites causing or driving NAFLD, can aid in categorization of patients with NAFLD into different metabolic subtypes and design personalised or subtype specific therapies for its management. 

Source: Chu H, Duan Y, Yang L, et al. Small metabolites, possible big changes: a microbiota-centered view of non-alcoholic fatty liver disease. Gut.2019;68:359-370.