Monocolonization with Bacteroides thetaiotaomicron exerts region-specific effects on Alzheimer’s disease-related traits in the murine brain

Bacteroides thetaiotaomicron (B. theta) dominates the gut microbiome of most mammals. This strictly anaerobic gut symbiont colonizes the mucus layer of host intestinal epithelial cells in both healthy and diseased conditions. Reduced neuronal and vagal afferent innervation observed in germ-free mice was found to be normalized by colonialization with B. theta. In addition to deficits in gut innervation, germ-free mice have been reported to have reduced neuronal number and neurotransmitter levels in the brain. Here, we investigated the hallmarks of Alzheimer’s disease (AD) in the brain of germ-free mice compared to mice mono-colonized with B. theta. We analysed the number of mature neurons, neurotransmitter transporters, amyloid precursor protein processing, and inflammatory status in three brain regions: the hippocampus, prefrontal cortex (PFC) and cerebellum. The hippocampus and the prefrontal cortex are regions thought to be highly susceptible to pathogenesis whereas the cerebellum is thought to be only mildly affected. Interestingly, secretion of neuroprotective APPsa decreased in hippocampus and remained unchanged in PFC, while levels were increased in the cerebellum in response to bacterial colonization. In addition, the number of presynaptic boutons increased in the hippocampus but remained unaffected in the cerebellum.