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


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Publication details

All authors or editorsDriuchina, 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 seriesmBio

ISSN2161-2129

eISSN2150-7511

Publication year2023

Publication date30/01/2023

Volume14

Issue number1

Article numbere02663-22

PublisherAmerican Society for Microbiology

Publication countryUnited States

Publication languageEnglish

DOIhttps://doi.org/10.1128/mbio.02663-22

Publication open accessOpenly available

Publication channel open accessOpen 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.


Keywordsinsulinliverinsulin resistancegastrointestinal microbiotafatty livermetabolic disorders

Free keywordsgut microbiota; insulin resistance; liver fat; metabolomics


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Ministry reportingYes

Reporting Year2023

JUFO rating2


Last updated on 2024-15-05 at 13:03