Microbiome-derived ethanol in nonalcoholic fatty liver disease
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Microbiome-derived ethanol in nonalcoholic fatty liver disease. / Meijnikman, Abraham S.; Davids, Mark; Herrema, Hilde; Aydin, Omrum; Tremaroli, Valentina; Rios-Morales, Melany; Levels, Han; Bruin, Sjoerd; de Brauw, Maurits; Verheij, Joanne; Kemper, Marleen; Holleboom, Adriaan G.; Tushuizen, Maarten E.; Schwartz, Thue W.; Nielsen, Jens; Brandjes, Dees; Dirinck, Eveline; Weyler, Jonas; Verrijken, An; De Block, Christophe E.M.; Vonghia, Luisa; Francque, Sven; Beuers, Ulrich; Gerdes, Victor E.A.; Bäckhed, Fredrik; Groen, Albert K.; Nieuwdorp, Max.
I: Nature Medicine, Bind 28, 2022, s. 2100-2106.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Microbiome-derived ethanol in nonalcoholic fatty liver disease
AU - Meijnikman, Abraham S.
AU - Davids, Mark
AU - Herrema, Hilde
AU - Aydin, Omrum
AU - Tremaroli, Valentina
AU - Rios-Morales, Melany
AU - Levels, Han
AU - Bruin, Sjoerd
AU - de Brauw, Maurits
AU - Verheij, Joanne
AU - Kemper, Marleen
AU - Holleboom, Adriaan G.
AU - Tushuizen, Maarten E.
AU - Schwartz, Thue W.
AU - Nielsen, Jens
AU - Brandjes, Dees
AU - Dirinck, Eveline
AU - Weyler, Jonas
AU - Verrijken, An
AU - De Block, Christophe E.M.
AU - Vonghia, Luisa
AU - Francque, Sven
AU - Beuers, Ulrich
AU - Gerdes, Victor E.A.
AU - Bäckhed, Fredrik
AU - Groen, Albert K.
AU - Nieuwdorp, Max
N1 - Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1038/s41591-022-02016-6
DO - 10.1038/s41591-022-02016-6
M3 - Journal article
C2 - 36216942
AN - SCOPUS:85139701303
VL - 28
SP - 2100
EP - 2106
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
ER -
ID: 322954212