Microbiome-derived ethanol in nonalcoholic fatty liver disease
Artikel i vetenskaplig tidskrift, 2022
To test the hypothesis that the gut microbiota of individuals with nonalcoholic fatty liver disease (NAFLD) produce enough ethanol to be a driving force in the development and progression of this complex disease, we performed one prospective clinical study and one intervention study. Ethanol was measured while fasting and 120 min after a mixed meal test (MMT) in 146 individuals. In a subset of 37 individuals and in an external validation cohort, ethanol was measured in portal vein blood. In an intervention study, ten individuals with NAFLD and ten overweight but otherwise healthy controls were infused with a selective alcohol dehydrogenase (ADH) inhibitor before an MMT. When compared to fasted peripheral blood, median portal vein ethanol concentrations were 187 (interquartile range (IQR), 17–516) times higher and increased with disease progression from 2.1 mM in individuals without steatosis to 8.0 mM in NAFL 21.0 mM in nonalcoholic steatohepatitis. Inhibition of ADH induced a 15-fold (IQR,1.6- to 20-fold) increase in peripheral blood ethanol concentrations in individuals with NAFLD, although this effect was abolished after antibiotic treatment. Specifically, Lactobacillaceae correlated with postprandial peripheral ethanol concentrations (Spearman’s rho, 0.42; P < 10−5) in the prospective study. Our data show that the first-pass effect obscures the levels of endogenous ethanol production, suggesting that microbial ethanol could be considered in the pathogenesis of this highly prevalent liver disease.
Författare
A. S. Meijnikman
Spaarne Gasthuis
Universiteit Van Amsterdam
Mark Davids
Universiteit Van Amsterdam
H. Herrema
Universiteit Van Amsterdam
O. Aydin
Universiteit Van Amsterdam
Spaarne Gasthuis
Valentina Tremaroli
Wallenberg Lab.
Melany Rios-Morales
Universiteit Van Amsterdam
Han Levels
Universiteit Van Amsterdam
S. C. Bruin
Spaarne Gasthuis
Maurits de Brauw
Spaarne Gasthuis
J. Verheij
Universiteit Van Amsterdam
Marleen Kemper
Universiteit Van Amsterdam
Adriaan G. Holleboom
Universiteit Van Amsterdam
Maarten E. Tushuizen
Universiteit Leiden
Thue W. Schwartz
Köpenhamns universitet
Jens B Nielsen
Chalmers, Biologi och bioteknik, Systembiologi
Dees Brandjes
Universiteit Van Amsterdam
Eveline Dirinck
UZA (Antwerp University Hospital)
Jonas Weyler
UZA (Antwerp University Hospital)
An Verrijken
UZA (Antwerp University Hospital)
Christophe E.M. De Block
UZA (Antwerp University Hospital)
Luisa Vonghia
UZA (Antwerp University Hospital)
Sven Francque
UZA (Antwerp University Hospital)
Ulrich Beuers
Universiteit Van Amsterdam
V. E.A. Gerdes
Universiteit Van Amsterdam
Spaarne Gasthuis
Fredrik Bäckhed
Wallenberg Lab.
Köpenhamns universitet
A. K. Groen
Universiteit Van Amsterdam
M. Nieuwdorp
Spaarne Gasthuis
Universiteit Van Amsterdam
Nature Medicine
1078-8956 (ISSN) 1546170x (eISSN)
Vol. 28 10 2100-2106Ämneskategorier
Annan klinisk medicin
Gastroenterologi
Näringslära
DOI
10.1038/s41591-022-02016-6
PubMed
36216942