The gut microbiota modulates brain network connectivity under physiological conditions and after acute brain ischemia
Markus Aswendt,
Claudia Green,
Rebecca Sadler,
Gemma Llovera,
Lauren Dzikowski,
Steffanie Heindl,
Mercedes Gomez de Agüero,
Michael Diedenhofen,
Stefanie Vogel,
Frederique Wieters,
Dirk Wiedermann,
Arthur Liesz,
Mathias Hoehn
Affiliations
Markus Aswendt
Department of Neurology, University of Cologne, Faculty of Medicine and University Hospital, 50923 Cologne, Germany; Corresponding author
Claudia Green
In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Gleuelerstrasse 50, 50931 Cologne, Germany
Rebecca Sadler
Institute for Stroke and Dementia Research (ISD), LMU Munich, Feodor-Lynen Strasse 17, 81377 Munich, Germany
Gemma Llovera
Institute for Stroke and Dementia Research (ISD), LMU Munich, Feodor-Lynen Strasse 17, 81377 Munich, Germany
Lauren Dzikowski
Institute for Stroke and Dementia Research (ISD), LMU Munich, Feodor-Lynen Strasse 17, 81377 Munich, Germany
Steffanie Heindl
Institute for Stroke and Dementia Research (ISD), LMU Munich, Feodor-Lynen Strasse 17, 81377 Munich, Germany
Mercedes Gomez de Agüero
Department for BioMedical Research (DBMR), University of Bern, 3012 Bern, Switzerland; Institute of Systems Immunology, Julius-Maximilians University of Würzburg, 97070 Würzburg, Germany
Michael Diedenhofen
In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Gleuelerstrasse 50, 50931 Cologne, Germany
Stefanie Vogel
In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Gleuelerstrasse 50, 50931 Cologne, Germany
Frederique Wieters
Department of Neurology, University of Cologne, Faculty of Medicine and University Hospital, 50923 Cologne, Germany
Dirk Wiedermann
In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Gleuelerstrasse 50, 50931 Cologne, Germany
Arthur Liesz
Institute for Stroke and Dementia Research (ISD), LMU Munich, Feodor-Lynen Strasse 17, 81377 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), 80807 Munich, Germany; Corresponding author
Mathias Hoehn
In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Gleuelerstrasse 50, 50931 Cologne, Germany; Corresponding author
Summary: The gut microbiome has been implicated as a key regulator of brain function in health and disease. But the impact of gut microbiota on functional brain connectivity is unknown. We used resting-state functional magnetic resonance imaging in germ-free and normally colonized mice under naive conditions and after ischemic stroke. We observed a strong, brain-wide increase of functional connectivity in germ-free animals. Graph theoretical analysis revealed significant higher values in germ-free animals, indicating a stronger and denser global network but with less structural organization. Breakdown of network function after stroke equally affected germ-free and colonized mice. Results from histological analyses showed changes in dendritic spine densities, as well as an immature microglial phenotype, indicating impaired microglia-neuron interaction in germ-free mice as potential cause of this phenomenon. These results demonstrate the substantial impact of bacterial colonization on brain-wide function and extend our so far mainly (sub) cellular understanding of the gut-brain axis.
