Microbiome-derived ethanol in nonalcoholic fatty liver disease

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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.

In: Nature Medicine, Vol. 28, 2022, p. 2100-2106.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Meijnikman, AS, Davids, M, Herrema, H, Aydin, O, Tremaroli, V, Rios-Morales, M, Levels, H, Bruin, S, de Brauw, M, Verheij, J, Kemper, M, Holleboom, AG, Tushuizen, ME, Schwartz, TW, Nielsen, J, Brandjes, D, Dirinck, E, Weyler, J, Verrijken, A, De Block, CEM, Vonghia, L, Francque, S, Beuers, U, Gerdes, VEA, Bäckhed, F, Groen, AK & Nieuwdorp, M 2022, 'Microbiome-derived ethanol in nonalcoholic fatty liver disease', Nature Medicine, vol. 28, pp. 2100-2106. https://doi.org/10.1038/s41591-022-02016-6

APA

Meijnikman, A. S., Davids, M., Herrema, H., Aydin, O., Tremaroli, V., Rios-Morales, M., Levels, H., Bruin, S., de Brauw, M., Verheij, J., Kemper, M., Holleboom, A. G., Tushuizen, M. E., Schwartz, T. W., Nielsen, J., Brandjes, D., Dirinck, E., Weyler, J., Verrijken, A., ... Nieuwdorp, M. (2022). Microbiome-derived ethanol in nonalcoholic fatty liver disease. Nature Medicine, 28, 2100-2106. https://doi.org/10.1038/s41591-022-02016-6

Vancouver

Meijnikman AS, Davids M, Herrema H, Aydin O, Tremaroli V, Rios-Morales M et al. Microbiome-derived ethanol in nonalcoholic fatty liver disease. Nature Medicine. 2022;28:2100-2106. https://doi.org/10.1038/s41591-022-02016-6

Author

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. / Microbiome-derived ethanol in nonalcoholic fatty liver disease. In: Nature Medicine. 2022 ; Vol. 28. pp. 2100-2106.

Bibtex

@article{54a0cff22cdc43fdaeb55557693c48ef,
title = "Microbiome-derived ethanol in nonalcoholic fatty liver disease",
abstract = "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{\textquoteright}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.",
author = "Meijnikman, {Abraham S.} and Mark Davids and Hilde Herrema and Omrum Aydin and Valentina Tremaroli and Melany Rios-Morales and Han Levels and Sjoerd Bruin and {de Brauw}, Maurits and Joanne Verheij and Marleen Kemper and Holleboom, {Adriaan G.} and Tushuizen, {Maarten E.} and Schwartz, {Thue W.} and Jens Nielsen and Dees Brandjes and Eveline Dirinck and Jonas Weyler and An Verrijken and {De Block}, {Christophe E.M.} and Luisa Vonghia and Sven Francque and Ulrich Beuers and Gerdes, {Victor E.A.} and Fredrik B{\"a}ckhed and Groen, {Albert K.} and Max Nieuwdorp",
note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
doi = "10.1038/s41591-022-02016-6",
language = "English",
volume = "28",
pages = "2100--2106",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "nature publishing group",

}

RIS

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