Arthur Liesz
Professor of Neurology
LMU University Munich
Arthur Liesz is a professor of experimental neurology at Ludwig Maximilian University Munich and board-certified neurologist at the University Medical Center. He received his training in neurology at the University of Heidelberg Medical Center, in addition he was trained in experimental immunology at the German Cancer Research Institute (DKFZ). His research interest is on immunological aspects of acute brain injury, working on the topic of brain-immune interaction after acute brain injuries for more than a decade. The research encompasses both sides of brain-immune interaction after stroke: the secondary neuroinflammatory reaction to brain damage and the impact of brain injury on the peripheral immune homeostasis. He is currently heading the Laboratory for Stroke-Immunology at the Institute for Stroke and Dementia Research (https://www.isd-research.de/liesz-lab), is principal investigator of the Excellence Cluster for Systems Neurology (www.synergy-munich.de) and coordinator of the German Stroke-Immunology network (www.immunostroke.de).
Abstract
Microbiota-derived SCFA Promote Alzheimer Disease Progression
Previous studies have identified a crucial role of the gut microbiome in modifying Alzheimer’s disease (AD) progression. However, the mechanisms of microbiome-brain interaction in AD, including the microbial mediators and their cellular targets in the brain, were so far unknown. Here, we identify microbiota-derived short chain fatty acids (SCFA) as key metabolites along the gut-brain axis in AD. Germ-free (GF) AD mice exhibit a substantially reduced Abeta plaque load and markedly reduced SCFA plasma concentrations; conversely, SCFA supplementation to GF AD mice was increased the Abeta plaque load to levels of conventionally colonized animals and SCFA supplementation to SPF mice even further exacerbated plaque load. We observed pronounced changes in microglial function associated with this phenomenon. SCFA modulated the microglial transcriptomic profile, reduced cellular Abeta uptake and upregulatied microglial ApoE expression. Taken together, our results demonstrate that microbiota-derived SCFA are the key mediators along the gut-brain axis which is most likely mediated via modulation of microglial function.