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

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van der Vossen , E W J , Bastos , D , Stols-Goncalves , D , de Goffau , M C , Davids , M , Pereira , J P B , Li Yim , A Y F , Henneman , P , Netea , M G , de Vos , W M , de Jonge , W , Groen , A K , Nieuwdorp , M & Levin , E 2021 , ' Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome ' , Gut Microbes , vol. 13 , no. 1 , 1993513 . https://doi.org/10.1080/19490976.2021.1993513

Title: Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome
Author: van der Vossen, Eduard W. J.; Bastos, Diogo; Stols-Goncalves, Daniela; de Goffau, Marcus C.; Davids, Mark; Pereira, Joao P. B.; Li Yim, Andrew Y. F.; Henneman, Peter; Netea, Mihai G.; de Vos, Willem M.; de Jonge, Wouter; Groen, Albert K.; Nieuwdorp, Max; Levin, Evgeni
Contributor organization: Willem Meindert Vos de / Principal Investigator
de Vos & Salonen group
Research Programs Unit
Departments of Faculty of Veterinary Medicine
HUMI - Human Microbiome Research
Date: 2021-01-01
Language: eng
Number of pages: 18
Belongs to series: Gut Microbes
ISSN: 1949-0976
DOI: https://doi.org/10.1080/19490976.2021.1993513
URI: http://hdl.handle.net/10138/337309
Abstract: 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.
Subject: Gut microbiome
machine learning
3121 General medicine, internal medicine and other clinical medicine
11832 Microbiology and virology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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