Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome

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 microbio...

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Autores principales:	Eduard W. J. van der Vossen, Diogo Bastos, Daniela Stols-Gonçalves, Marcus C. de Goffau, Mark Davids, Joao P. B. Pereira, Andrew Y. F. Li Yim, Peter Henneman, Mihai G. Netea, Willem M. de Vos, Wouter de Jonge, Albert K. Groen, Max Nieuwdorp, Evgeni Levin
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	gut microbiome metabolome fmt epigenetics machine learning Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/f28625718d0d47aca2dbfdcdd0f83f74
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spelling	oai:doaj.org-article:f28625718d0d47aca2dbfdcdd0f83f742021-11-11T14:23:42ZEffects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome1949-09761949-098410.1080/19490976.2021.1993513https://doaj.org/article/f28625718d0d47aca2dbfdcdd0f83f742021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/19490976.2021.1993513https://doaj.org/toc/1949-0976https://doaj.org/toc/1949-0984Accumulating 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.Eduard W. J. van der VossenDiogo BastosDaniela Stols-GonçalvesMarcus C. de GoffauMark DavidsJoao P. B. PereiraAndrew Y. F. Li YimPeter HennemanMihai G. NeteaWillem M. de VosWouter de JongeAlbert K. GroenMax NieuwdorpEvgeni LevinTaylor & Francis Grouparticlegut microbiomemetabolomefmtepigeneticsmachine learningDiseases of the digestive system. GastroenterologyRC799-869ENGut Microbes, Vol 13, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	gut microbiome metabolome fmt epigenetics machine learning Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	gut microbiome metabolome fmt epigenetics machine learning Diseases of the digestive system. Gastroenterology RC799-869 Eduard W. J. van der Vossen Diogo Bastos Daniela Stols-Gonçalves Marcus C. de Goffau Mark Davids Joao P. B. Pereira Andrew Y. F. Li Yim Peter Henneman Mihai G. Netea Willem M. de Vos Wouter de Jonge Albert K. Groen Max Nieuwdorp Evgeni Levin Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome
description	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.
format	article
author	Eduard W. J. van der Vossen Diogo Bastos Daniela Stols-Gonçalves Marcus C. de Goffau Mark Davids Joao P. B. Pereira Andrew Y. F. Li Yim Peter Henneman Mihai G. Netea Willem M. de Vos Wouter de Jonge Albert K. Groen Max Nieuwdorp Evgeni Levin
author_facet	Eduard W. J. van der Vossen Diogo Bastos Daniela Stols-Gonçalves Marcus C. de Goffau Mark Davids Joao P. B. Pereira Andrew Y. F. Li Yim Peter Henneman Mihai G. Netea Willem M. de Vos Wouter de Jonge Albert K. Groen Max Nieuwdorp Evgeni Levin
author_sort	Eduard W. J. van der Vossen
title	Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome
title_short	Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome
title_full	Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome
title_fullStr	Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome
title_full_unstemmed	Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome
title_sort	effects of fecal microbiota transplant on dna methylation in subjects with metabolic syndrome
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/f28625718d0d47aca2dbfdcdd0f83f74
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Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome

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