Recent Advances of Microbiome-Associated Metabolomics Profiling in Liver Disease: Principles, Mechanisms, and Applications

Abstract

Advances in high-throughput screening of metabolic stability in liver and gut microbiota are able to identify and quantify small-molecule metabolites (metabolome) in different cellular microenvironments that are closest to their phenotypes. Metagenomics and metabolomics are largely recognized to be the “-omics” disciplines for clinical therapeutic screening. Here, metabolomics activity screening in liver disease (LD) and gut microbiomes has significantly delivered the integration of metabolomics data (i.e., a set of endogenous metabolites) with metabolic pathways in cellular environments that can be tested for biological functions (i.e., phenotypes). A growing literature in LD and gut microbiomes reports the use of metabolites as therapeutic targets or biomarkers. Although growing evidence connects liver fibrosis, cirrhosis, and hepatocellular carcinoma, the genetic and metabolic factors are still mainly unknown. Herein, we reviewed proof-of-concept mechanisms for metabolomics-based LD and gut microbiotas’ role from several studies (nuclear magnetic resonance, gas/lipid chromatography, spectroscopy coupled with mass spectrometry, and capillary electrophoresis). A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to improve liver health.

Duodenal Microbiome and Serum Metabolites Predict Hepatocellular Carcinoma in a Multicenter Cohort of Patients with Cirrhosis

“…There is a growing body of evidence stating the importance of metabolomics profiling in both liver disease and cancer [12,13]. Given the growing recognition for the importance of metabolic activity of gut microbiota in HCC pathogenesis, we examined biogenic amines and bile acid concentration in relation to HCC risk.…”

“…In addition to the microbiome, there is also a growing body of literature that has shown microbe-associated metabolites to be important biomarkers and affecters of liver disease and cancer [12,13]. Microbe-associated metabolites such as bile acids, damage-associated molecular patterns (DAMPs), amino acids, and short-chain fatty acids can be released into the portal circulation and absorbed in the liver causing changes in immune function, cytokine release, and cell signaling [13][14][15]. Therefore, the study of these microbe-associated metabolites is just as important as the study of the microbes themselves.…”

Early Time-Restricted Feeding Amends Circadian Clock Function and Improves Metabolic Health in Male and Female Nile Grass Rats

“…This study, therefore, aimed to determine the effect of early and late TRF on high-fat diet-induced metabolic changes in male and female NGR. As the liver is the first peripheral target organ for food-induced circadian phase resetting and the main regulator of systemic metabolic homeostasis [19,20], hepatic metabolites were quantified to provide insights into the metabolic manifestations of TRF treatment [21].…”

The Interaction between the Gut Microbiome and Bile Acids in Cardiometabolic Diseases

“…Significant advances have been made linking the (gut-derived) metabolome to NAFLD and NASH. This link has also been found through the interaction of the immune system and the gut microbiota and is reviewed elsewhere [42][43][44][45].…”