Identification of Gut Microbial Lysine and Histidine Degradation and CYP-Dependent Metabolites as Biomarkers of Fatty Liver Disease
Driuchina, A., Hintikka, J., Lehtonen, M., Keski-Rahkonen, P., O’Connell, T., Juvonen, R., Kuula, J., Hakkarainen, A., Laukkanen, J. A., Mäkinen, E., Lensu, S., Pietiläinen, K. H., & Pekkala, S. (2023). Identification of Gut Microbial Lysine and Histidine Degradation and CYP-Dependent Metabolites as Biomarkers of Fatty Liver Disease. mBio, 14(1), Article e02663-22. https://doi.org/10.1128/mbio.02663-22
© 2023 Driuchina et al.
Numerous studies have described specific metabolites as biomarkers ofsevere liver diseases, but very few have measured gut microbiota (GM)-produced metab-olites in fatty liver disease. We aimed atfinding GM signatures and metabolite markersin plasma and feces related to high liver fat content. Based on imaging, we dividedstudy participants into low (,5%, LF,n= 25) and high (.5%, HF,n= 39) liver fatgroups. Fecal (LFn= 14, HFn= 25) and plasma (LFn= 11, HFn= 7) metabolomes ofsubsets of participants were studied using liquid chromatography/high resolution massspectrometry. The GM were analyzed using 16S rRNA gene sequencing. Additionally,blood clinical variables and diet were studied. Dyslipidemia, higher liver enzymes and in-sulin resistance characterized the HF group. No major differences in diet were foundbetween the groups. In the GM, the HF group had lower abundance ofBacteroidesandPrevotellaceae NK3B31 group than the LF group after adjusting for metformin use orobesity. In feces, the HF group had higher levels of lysine and histidine degradationproducts, while 6-hydroxybetatestosterone (metabolized by CYP3A4) was low. Higherplasma levels of caffeine and its metabolites in the HF group indicate that the activity ofhepatic CYP1A2 was lower than in the LF group. Our results suggest, that low fecalPrevotellaceae NK3B31 andBacteroidesabundance, and increased lysine and histidinedegradation may serve as GM biomarkers of high liver fat. Altered plasma caffeinemetabolites and lowered testosterone metabolism may specify decreased CYP activities,and their potential utility, as biomarkers of fatty liver disease. ...
PublisherAmerican Society for Microbiology
ISSN Search the Publication Forum2161-2129
Publication in research information system
MetadataShow full item record
Related funder(s)Academy of Finland
Funding program(s)Academy Project, AoF; Academy Research Fellow, AoF
Additional information about fundingSatu Pekkala was funded by the Academy of Finland (grant numbers 308042 and 349264), and by the ERVA funding of the Southwest Finland Health Care District. The study was also supported by the Academy of Finland funded Profiling of University of Jyväskylä and the Faculty of Sport and Health Sciences: Physical activity through life span (PACTS2). Kirsi H. Pietiläinen was funded by the Academy of Finland (grant numbers 335443, 314383, 272376, 266286), Finnish Medical Foundation, Gyllenberg Foundation, Novo Nordisk Foundation (grant numbers NNF20OC0060547, NNF17OC0027232, NNF10OC1013354), Finnish Diabetes Research Foundation, University of Helsinki, and Helsinki University Hospital Government Research Funds. Sanna Lensu was funded from the projects by the Academy of Finland (grant ID 316966 and 321522), and grants from Jenny & Artturi Wihuri Foundation and the Central Finland Regional Fund of the Finnish Cultural Foundation. ...
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