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 N. Vogel, Frederique Wieters, Dirk Wiedermann, Arthur Liesz, Mathias Hoehn
Abstract
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.