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Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer's disease.
Martinelli, Filippo; Heinken, Almut; Henning, Ann-Kristin; Ulmer, Maria A; Hensen, Tim; González, Antonio; Arnold, Matthias; Asthana, Sanjay; Budde, Kathrin; Engelman, Corinne D; Estaki, Mehrbod; Grabe, Hans-Jörgen; Heston, Margo B; Johnson, Sterling; Kastenmüller, Gabi; Martino, Cameron; McDonald, Daniel; Rey, Federico E; Kilimann, Ingo; Peters, Olive; Wang, Xiao; Spruth, Eike Jakob; Schneider, Anja; Fliessbach, Klaus; Wiltfang, Jens; Hansen, Niels; Glanz, Wenzel; Buerger, Katharina; Janowitz, Daniel; Laske, Christoph; Munk, Matthias H; Spottke, Annika; Roy, Nina; Nauck, Matthias; Teipel, Stefan; Knight, Rob; Kaddurah-Daouk, Rima F; Bendlin, Barbara B; Hertel, Johannes; Thiele, Ines.
Afiliación
  • Martinelli F; School of Medicine, University of Galway, Galway, Ireland.
  • Heinken A; The Ryan Institute, University of Galway, Galway, Ireland.
  • Henning AK; School of Medicine, University of Galway, Galway, Ireland.
  • Ulmer MA; The Ryan Institute, University of Galway, Galway, Ireland.
  • Hensen T; Inserm UMRS 1256 NGERE, University of Lorraine, Nancy, France.
  • González A; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Arnold M; Institute of Computational Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
  • Asthana S; School of Medicine, University of Galway, Galway, Ireland.
  • Budde K; The Ryan Institute, University of Galway, Galway, Ireland.
  • Engelman CD; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
  • Estaki M; Institute of Computational Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
  • Grabe HJ; Department of Psychiatry and Behavioural Sciences, Duke University, Durham, NC, USA.
  • Heston MB; Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, USA.
  • Johnson S; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Kastenmüller G; Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
  • Martino C; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
  • McDonald D; German Center of Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany.
  • Rey FE; Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, USA.
  • Kilimann I; Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, USA.
  • Peters O; Institute of Computational Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
  • Wang X; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
  • Spruth EJ; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
  • Schneider A; Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
  • Fliessbach K; German Center of Neurodegenerative Diseases (DZNE), Rostock, Germany.
  • Wiltfang J; Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany.
  • Hansen N; German Center of Neurodegenerative Diseases (DZNE), Berlin, Germany.
  • Glanz W; Department of Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • Buerger K; Department of Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • Janowitz D; German Center of Neurodegenerative Diseases (DZNE), Berlin, Germany.
  • Laske C; Department of Psychiatry and Psychotherapy, Charité, Berlin, Germany.
  • Munk MH; German Center of Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Spottke A; Department of Neurology, University of Bonn, Bonn, Germany.
  • Roy N; German Center of Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Nauck M; Department of Neurology, University of Bonn, Bonn, Germany.
  • Teipel S; German Center of Neurodegenerative Diseases (DZNE), Goettingen, Germany.
  • Knight R; Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany.
  • Kaddurah-Daouk RF; Neurosciences and Signaling Group, Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, Aveiro, Portugal.
  • Bendlin BB; Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany.
  • Hertel J; German Center of Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
  • Thiele I; German Center of Neurodegenerative Diseases (DZNE), Munich, Germany.
Sci Rep ; 14(1): 6095, 2024 03 13.
Article en En | MEDLINE | ID: mdl-38480804
ABSTRACT
In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and controls, revealing decreased formate and fumarate concentrations in AD. Additionally, we utilised whole-genome sequencing (WGS) data obtained from a separate group of individuals with AD and controls. This information allowed us to create and investigate host-microbiome personalised whole-body metabolic models. Notably, AD individuals displayed diminished formate microbial secretion in these models. Additionally, we identified specific reactions responsible for the production of formate in the host, and interestingly, these reactions were linked to genes that have correlations with AD. This study suggests formate as a possible early AD marker and highlights genetic and microbiome contributions to its production. The reduced formate secretion and its genetic associations point to a complex connection between gut microbiota and AD. This holistic understanding might pave the way for novel diagnostic and therapeutic avenues in AD management.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer / Microbiota / Microbioma Gastrointestinal Límite: Humans Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Irlanda
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer / Microbiota / Microbioma Gastrointestinal Límite: Humans Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Irlanda