Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome
| Autor: | Max Nieuwdorp, Eduard W. J. van der Vossen, Diogo Mendes Bastos, Mihai G. Netea, Andrew Y. F. Li Yim, Mark Davids, Evgeni Levin, Peter Henneman, Marcus C. de Goffau, Albert K. Groen, João P. Belo Pereira, Wouter J. de Jonge, Willem M. de Vos, Daniela Stols-Gonçalves |
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| Přispěvatelé: | Willem Meindert Vos de / Principal Investigator, de Vos & Salonen group, Research Programs Unit, Departments of Faculty of Veterinary Medicine, HUMI - Human Microbiome Research, Graduate School, Vascular Medicine, Experimental Vascular Medicine, Center of Experimental and Molecular Medicine, Human Genetics, ACS - Atherosclerosis & ischemic syndromes, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ARD - Amsterdam Reproduction and Development, Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, ACS - Diabetes & metabolism |
| Rok vydání: | 2021 |
| Předmět: |
Male
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] RC799-869 Gut flora 0302 clinical medicine Epigenomics Metabolic Syndrome 11832 Microbiology and virology 0303 health sciences INSULIN SENSITIVITY Microfilament Proteins GUT MICROBIOTA Gastroenterology Fecal Microbiota Transplantation Middle Aged Diseases of the digestive system. Gastroenterology 3. Good health Infectious Diseases machine learning OBESITY DNA methylation Female metabolome Research Article Research Paper Adult Microbiology (medical) DONOR FECES CROSSTALK IMPROVEMENT Biology Microbiology Young Adult 03 medical and health sciences Insulin resistance All institutes and research themes of the Radboud University Medical Center INTESTINAL MICROBIOTA Metabolome medicine Humans Epigenetics Aged 030304 developmental biology FMT Gut microbiome epigenetics BacGen Epigenome DNA Methylation medicine.disease biology.organism_classification GENE Gastrointestinal Microbiome DISCOVERY 3121 General medicine internal medicine and other clinical medicine Immunology Insulin Resistance Metabolic syndrome 030217 neurology & neurosurgery |
| Zdroj: | Gut Microbes, 13, 1 Gut Microbes, 13 Gut microbes, 13(1):1993513. Landes Bioscience Gut Microbes 13 (2021) 1 Gut Microbes, Vol 13, Iss 1 (2021) Gut Microbes, 13(1) Gut Microbes article-version (VoR) Version of Record |
| ISSN: | 1949-0976 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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