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 - Funding Information: E. vd V. is supported by a CVON INCONTROL-2 grant. M.N. is supported by a personal ZONMW VICI grant 2020 (09150182010020). M.S.M. is supported by a grant from Innovation Fund Denmark [7038-00008B]. A.G.H. is supported by the Amsterdam UMC Fellowship grant, the Amsterdam UMC Innovation grant, two grants from the Dutch Gastroenterology Foundation MLDS and two grants from Holland~Health TKI‐PPP. Publisher Copyright: © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2023/12/31
Y1 - 2023/12/31
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 - multi-omics analysis
KW - non-alcoholic fatty liver disease (NAFLD)
UR - http://www.scopus.com/inward/record.url?scp=85161961018&partnerID=8YFLogxK
U2 - https://doi.org/10.1080/19490976.2023.2223330
DO - https://doi.org/10.1080/19490976.2023.2223330
M3 - Article
C2 - 37317027
SN - 1949-0976
VL - 15
SP - 2223330
JO - Gut Microbes
JF - Gut Microbes
IS - 1
M1 - 2223330
ER -