TY - JOUR
T1 - Faecal Microbiota transplantation affects liver DNA methylation in Non-alcoholic fatty liver disease
T2 - a multi-omics approach
AU - Stols-Gonçalves, Daniela
AU - Mak, Anne Linde
AU - Madsen, Mette S.
AU - van der Vossen, Eduard W. J.
AU - Bruinstroop, Eveline
AU - Henneman, Peter
AU - Mol, Femke
AU - Scheithauer, Torsten P.M.
AU - Smits, Loek
AU - Witjes, Julia
AU - Meijnikman, Abraham Stijn
AU - Verheij, Joanne
AU - Nieuwdorp, Max
AU - Holleboom, Adriaan G.
AU - Levin, Evgeni
N1 - Publisher Copyright:
© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2023
Y1 - 2023
N2 - Individuals with nonalcoholic fatty liver disease (NAFLD) have an altered
gut microbiota composition. Moreover, hepatic DNA methylation may be
altered in the state of NAFLD. Using a fecal microbiota transplantation
(FMT) intervention, we aimed to investigate whether a change in gut
microbiota composition relates to altered liver DNA methylation in
NAFLD. Moreover, we assessed whether plasma metabolite profiles altered
by FMT relate to changes in liver DNA methylation. Twenty-one
individuals with NAFLD underwent three 8-weekly vegan allogenic donor (n = 10) or autologous (n = 11)
FMTs. We obtained hepatic DNA methylation profiles from paired liver
biopsies of study participants before and after FMTs. We applied a
multi-omics machine learning approach to identify changes in the gut
microbiome, peripheral blood metabolome and liver DNA methylome, and
analyzed cross-omics correlations. Vegan allogenic donor FMT compared to
autologous FMT induced distinct differential changes in I) gut
microbiota profiles, including increased abundance of Eubacterium siraeum and potential probiotic Blautia wexlerae;
II) plasma metabolites, including altered levels of
phenylacetylcarnitine (PAC) and phenylacetylglutamine (PAG) both from
gut-derived phenylacetic acid, and of several choline-derived long-chain
acylcholines; and III) hepatic DNA methylation profiles, most
importantly in Threonyl-TRNA Synthetase 1 (TARS) and Zinc finger protein 57 (ZFP57). Multi-omics analysis showed that Gemmiger formicillis and Firmicutes bacterium_CAG_170 positively correlated with both PAC and PAG. E siraeum negatively correlated with DNA methylation of cg16885113 in ZFP57.
Alterations in gut microbiota composition by FMT caused widespread
changes in plasma metabolites (e.g. PAC, PAG, and choline-derived
metabolites) and liver DNA methylation profiles in individuals with
NAFLD. These results indicate that FMTs might induce metaorganismal
pathway changes, from the gut bacteria to the liver.
AB - Individuals with nonalcoholic fatty liver disease (NAFLD) have an altered
gut microbiota composition. Moreover, hepatic DNA methylation may be
altered in the state of NAFLD. Using a fecal microbiota transplantation
(FMT) intervention, we aimed to investigate whether a change in gut
microbiota composition relates to altered liver DNA methylation in
NAFLD. Moreover, we assessed whether plasma metabolite profiles altered
by FMT relate to changes in liver DNA methylation. Twenty-one
individuals with NAFLD underwent three 8-weekly vegan allogenic donor (n = 10) or autologous (n = 11)
FMTs. We obtained hepatic DNA methylation profiles from paired liver
biopsies of study participants before and after FMTs. We applied a
multi-omics machine learning approach to identify changes in the gut
microbiome, peripheral blood metabolome and liver DNA methylome, and
analyzed cross-omics correlations. Vegan allogenic donor FMT compared to
autologous FMT induced distinct differential changes in I) gut
microbiota profiles, including increased abundance of Eubacterium siraeum and potential probiotic Blautia wexlerae;
II) plasma metabolites, including altered levels of
phenylacetylcarnitine (PAC) and phenylacetylglutamine (PAG) both from
gut-derived phenylacetic acid, and of several choline-derived long-chain
acylcholines; and III) hepatic DNA methylation profiles, most
importantly in Threonyl-TRNA Synthetase 1 (TARS) and Zinc finger protein 57 (ZFP57). Multi-omics analysis showed that Gemmiger formicillis and Firmicutes bacterium_CAG_170 positively correlated with both PAC and PAG. E siraeum negatively correlated with DNA methylation of cg16885113 in ZFP57.
Alterations in gut microbiota composition by FMT caused widespread
changes in plasma metabolites (e.g. PAC, PAG, and choline-derived
metabolites) and liver DNA methylation profiles in individuals with
NAFLD. These results indicate that FMTs might induce metaorganismal
pathway changes, from the gut bacteria to the liver.
KW - DNA methylation
KW - Faecal microbiota transplantation (FMT)
KW - Non-alcoholic fatty liver disease (NAFLD)
KW - Multi-omics analysis
U2 - 10.1080/19490976.2023.2223330
DO - 10.1080/19490976.2023.2223330
M3 - Journal article
C2 - 37317027
AN - SCOPUS:85161961018
SN - 1949-0976
VL - 15
JO - Gut Microbes
JF - Gut Microbes
IS - 1
M1 - 2223330
ER -