Numerous studies have described specific metabolites as
biomarkers of severe
liver diseases, but very few have measured gut microbiota (GM)-produced metabolites in
fatty liver disease. We aimed at finding GM signatures and metabolite markers in plasma and feces related to high liver fat content. Based on imaging, we divided study participants into low (<5%, LF, n = 25) and high (>5%, HF, n = 39) liver fat groups. Fecal (LF n = 14, HF n = 25) and plasma (LF n = 11, HF n = 7) metabolomes of subsets of participants were studied using liquid chromatography/high resolution mass spectrometry. The GM were analyzed using
16S rRNA gene sequencing. Additionally, blood clinical variables and diet were studied.
Dyslipidemia, higher liver
enzymes and
insulin resistance characterized the HF group. No major differences in diet were found between the groups. In the GM, the HF group had lower abundance of Bacteroides and Prevotellaceae NK3B31 group than the LF group after adjusting for
metformin use or
obesity. In feces, the HF group had higher levels of
lysine and
histidine degradation products, while 6-hydroxybetatestosterone (metabolized by
CYP3A4) was low. Higher plasma levels of
caffeine and its metabolites in the HF group indicate that the activity of hepatic
CYP1A2 was lower than in the LF group. Our results suggest, that low fecal Prevotellaceae NK3B31 and Bacteroides abundance, and increased
lysine and
histidine degradation may serve as GM
biomarkers of high liver fat. Altered plasma
caffeine metabolites and lowered
testosterone metabolism may specify decreased CYP activities, and their potential utility, as
biomarkers of
fatty liver disease. IMPORTANCE Because the high prevalence of
nonalcoholic fatty liver disease sets diagnostic challenges to health care, identification of new
biomarkers of the disease that in the future could have potential utility as diagnostic
biomarkers of high liver fat content is important. Our results show that increased
amino acid degradation products in the feces may be such
biomarkers. In the blood, molecules that indicate defective hepatic metabolic
enzyme activities were identified in individuals with high liver fat content.