A1 Journal article (refereed)
Identification of Gut Microbial Lysine and Histidine Degradation and CYP-Dependent Metabolites as Biomarkers of Fatty Liver Disease (2023)
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
JYU authors or editors
Publication details
All authors or editors: Driuchina, Anastasiia; Hintikka, Jukka; Lehtonen, Marko; Keski-Rahkonen, Pekka; O’Connell, Thomas; Juvonen, Risto; Kuula, Juho; Hakkarainen, Antti; Laukkanen, Jari A.; Mäkinen, Elina; et al.
Journal or series: mBio
ISSN: 2161-2129
eISSN: 2150-7511
Publication year: 2023
Publication date: 30/01/2023
Volume: 14
Issue number: 1
Article number: e02663-22
Publisher: American Society for Microbiology
Publication country: United States
Publication language: English
DOI: https://doi.org/10.1128/mbio.02663-22
Publication open access: Openly available
Publication channel open access: Open Access channel
Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/85374
Abstract
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.
Keywords: insulin; liver; insulin resistance; gastrointestinal microbiota; fatty liver; metabolic disorders
Free keywords: gut microbiota; insulin resistance; liver fat; metabolomics
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Ministry reporting: Yes
VIRTA submission year: 2023
JUFO rating: 2
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- Behaviour change, health, and well-being across the lifespan (University of Jyväskylä JYU) BC-Well
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