Gut microbiota mediated molecular events and therapy in liver diseases

Table 1 Summary of metabolites associated with liver diseases

Liver disease	Sample sources	Metabolites	Gut microbiota	Functions in liver disease	Ref.
NAFLD	Serum	3-(4-hydroxyphenyl) lactate	Abundance in bacteria Firmicutes, Bacteroidetes, Proteobacteria	It is positively associated with liver fibrosis	[56]
NAFLD	Serum	Eight lipids (5α-androstan-3β monosulfate, pregnanediol-3-glucuronide, androsterone sulfate, epiandrosterone sulfate, palmitoleate, dehydroisoandrosterone sulfate, 5α-androstan-3β disulfate, glycocholate), one amino acid (taurine) and one carbohydrate (fucose)	Without special bacterial species	Glycocholate is positively associated with advanced liver fibrosis	[57]
FL	Stool	Tryptamine and I3A	Microbiota-dependent without exact bacterial species	They inhibited the pro-inflammatory cytokines in macrophages and hepatocytes. I3A attenuated inflammatory responses under lipid loading and reduced the expression of fatty acid synthase and sterol regulatory element-binding protein-1c	[58]
FL	Stool	Gly-MCA	Increases in the ratio of Bacteroidetes/Firmicutes	Gly-MCA is an intestinal FXR antagonist, which inhibits HFD-induced fatty liver	[59]
HCC	Stool	Secondary bile acids, such as deoxycholic acid	Increase of Bacteroides and Clostridium cluster XVIII. Low of Streptococcus, Bifidobacterium, and Prevotella	Bile acids derived from the increased microbiota promote the progression of HCC	[52]
HCC	Stool	Bile acids, such as primary bile acid CDCA	Increase in Clostridium species	Removing gram-positive bacteria by antibiotic treatment with vancomycin, which contains the bacteria mediating primary-to-secondary bile acid conversion, was sufficient to induce hepatic NKT cell accumulation and decrease liver tumor growth	[15]
Liver cirrhosis	Stool	Glutamic acid, fumaric acid, 4-aminobutyric acid, succinic acid, isoleucine, valine, lactic acid, mannitol, sorbitol, carbamide, 4-aminobutyric acid, 5-aminopylamine, glutamate, proline, hydroxyproline	High of Enterobacteriaceae and Veillonella. Low of Bacteroidetes	These metabolites are involved in the KEGG pathway in nitrogen metabolism alanine, aspartate, and glutamate metabolism, and valine, leucine, and isoleucine, pantothenate and CoA biosynthesis, glycolysis/ gluconeogenesis, fructose and mannose metabolism, arginine and proline metabolism	[60]
NAFL or NASH	Stool	1-pentanol and 2-butanone, and 4-methyl-2-pentanone	Abundance in Oscillospira, Dorea, and Ruminococcus	The results indicated that significantly lower levels of Oscillospira and higher levels of 1-pentanol and 2-butanone in NAFL patients compared to healthy ones. In NASH, lower levels of Oscillospira were associated with a higher abundance of Dorea and Ruminococcus and higher levels of 2-butanone and 4-methyl-2-pentanone compared to CTRLs	[4]
ALD	Stool, urine	e.g., SCFAs butyrate and propionate	The main harmful bacterial species included altered Bacteroides phylum as well as Bilophila, Alistipes, Butyricimonas, Clostridium, Proteus, and Escherichia coli. Faecalibacterium	Metabolites are affected by chronic ethanol feeding or consumption, including amino acids, steroids and their derivatives, fatty acids and conjugates	[61]

NAFLD: Nonalcoholic fatty liver disease; FL: Fatty liver; I3A: Indole-3-acetate; Gly-MCA: Glycine-β-muricholic acid; HFD: High-fat diet; HCC: Hepatocellular carcinoma; CDCA: Chenodeoxycholic acid; NAFL: Nonalcoholic fatty liver; NASH: Nonalcoholic steatohepatitis; ALD: Alcohol-induced liver disease; SCFAs: Short-chain fatty acids.