TY - JOUR
T1 - Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome
AU - van der Vossen, Eduard W. J.
AU - Bastos, Diogo
AU - Stols-Gonçalves, Daniela
AU - de Goffau, Marcus C.
AU - Davids, Mark
AU - Pereira, Joao P. B.
AU - Li Yim, Andrew Y. F.
AU - Henneman, Peter
AU - Netea, Mihai G.
AU - de Vos, Willem M.
AU - de Jonge, Wouter
AU - Groen, Albert K.
AU - Nieuwdorp, Max
AU - Levin, Evgeni
N1 - Funding Information: E. vd V. is supported by a CVON INCONTROL-2 grant [2018.27]. W.M. de V. is supported by the 2008 Spinoza grant and the SIAM Gravitation Grant [024.002.002] of the Netherlands Organization for Scientific Research. A.Y.F.L.Y. was supported by the European Commission H2020 grant [SEP-210163258]. MN is supported by a ZONMW VICI grant 2020 [09150182010020]. This research has been also supported by ZonMw for Technology Hotel grant [40–43500–98–5007]. Funding Information: This work was supported by the CVON INCONTROL-2 [2018.27]; H2020 Grant [SEP?210163258]; ZONMW VICI Grant [09150182010020]; Spinoza grant and SIAM gravitation Grant [024.002.002]; ZonMw for Technology Hotel grant [40?43500?98?5007]. E. vd V. is supported by a CVON INCONTROL-2 grant [2018.27]. W.M. de V. is supported by the 2008 Spinoza grant and the SIAM Gravitation Grant [024.002.002] of the Netherlands Organization for Scientific Research. A.Y.F.L.Y. was supported by the European Commission H2020 grant [SEP-210163258]. MN is supported by a ZONMW VICI grant 2020 [09150182010020]. This research has been also supported by ZonMw for Technology Hotel grant [40?43500?98?5007]. Publisher Copyright: © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2021
Y1 - 2021
N2 - Accumulating evidence shows that microbes with their theater of activity residing within the human intestinal tract (i.e., the gut microbiome) influence host metabolism. Some of the strongest results come from recent fecal microbial transplant (FMT) studies that relate changes in intestinal microbiota to various markers of metabolism as well as the pathophysiology of insulin resistance. Despite these developments, there is still a limited understanding of the multitude of effects associated with FMT on the general physiology of the host, beyond changes in gut microbiome composition. We examined the effect of either allogenic (lean donor) or autologous FMTs on the gut microbiome, plasma metabolome, and epigenomic (DNA methylation) reprogramming in peripheral blood mononuclear cells in individuals with metabolic syndrome measured at baseline (pre-FMT) and after 6 weeks (post-FMT). Insulin sensitivity was determined with a stable isotope-based 2 step hyperinsulinemic clamp and multivariate machine learning methodology was used to uncover discriminative microbes, metabolites, and DNA methylation loci. A larger gut microbiota shift was associated with an allogenic than with autologous FMT. Furthemore, the data results of the the allogenic FMT group data indicates that the introduction of new species can potentially modulate the plasma metabolome and (as a result) the epigenome. Most notably, the introduction of Prevotella ASVs directly correlated with methylation of AFAP1, a gene involved in mitochondrial function, insulin sensitivity, and peripheral insulin resistance (Rd, rate of glucose disappearance). FMT was found to have notable effects on the gut microbiome but also on the host plasma metabolome and the epigenome of immune cells providing new avenues of inquiry in the context of metabolic syndrome treatment for the manipulation of host physiology to achieve improved insulin sensitivity.
AB - Accumulating evidence shows that microbes with their theater of activity residing within the human intestinal tract (i.e., the gut microbiome) influence host metabolism. Some of the strongest results come from recent fecal microbial transplant (FMT) studies that relate changes in intestinal microbiota to various markers of metabolism as well as the pathophysiology of insulin resistance. Despite these developments, there is still a limited understanding of the multitude of effects associated with FMT on the general physiology of the host, beyond changes in gut microbiome composition. We examined the effect of either allogenic (lean donor) or autologous FMTs on the gut microbiome, plasma metabolome, and epigenomic (DNA methylation) reprogramming in peripheral blood mononuclear cells in individuals with metabolic syndrome measured at baseline (pre-FMT) and after 6 weeks (post-FMT). Insulin sensitivity was determined with a stable isotope-based 2 step hyperinsulinemic clamp and multivariate machine learning methodology was used to uncover discriminative microbes, metabolites, and DNA methylation loci. A larger gut microbiota shift was associated with an allogenic than with autologous FMT. Furthemore, the data results of the the allogenic FMT group data indicates that the introduction of new species can potentially modulate the plasma metabolome and (as a result) the epigenome. Most notably, the introduction of Prevotella ASVs directly correlated with methylation of AFAP1, a gene involved in mitochondrial function, insulin sensitivity, and peripheral insulin resistance (Rd, rate of glucose disappearance). FMT was found to have notable effects on the gut microbiome but also on the host plasma metabolome and the epigenome of immune cells providing new avenues of inquiry in the context of metabolic syndrome treatment for the manipulation of host physiology to achieve improved insulin sensitivity.
KW - FMT
KW - Gut microbiome
KW - epigenetics
KW - machine learning
KW - metabolome
UR - http://www.scopus.com/inward/record.url?scp=85118938221&partnerID=8YFLogxK
U2 - https://doi.org/10.1080/19490976.2021.1993513
DO - https://doi.org/10.1080/19490976.2021.1993513
M3 - Article
C2 - 34747338
SN - 1949-0976
VL - 13
JO - Gut Microbes
JF - Gut Microbes
IS - 1
M1 - 1993513
ER -