Is acquired Piezo2 channelopathy the critical impairment of the brain axes and dysbiosis?

The current speculative review puts into perspectives how transplanted altered microbiota from Alzheimer’s patients initiates the impairment of the microbiota-gut-brain axis of the healthy recipient, leading to impaired cognition primarily arising from the hippocampus, dysfunctional adult hippocampal neurogenesis, dysregulated systemic inflammation, long-term spatial memory impairment or chronic pain with hippocampal involvement. The underlying mechanism likely caused by altered microbiota induced acquired Piezo2 channelopathy on enterochromaffin cells that in return impairs the ultrafast long-range proton-based oscillatory synchronization to the hippocampus. Therefore, the intact microbiota-gut-brain axis could be responsible for the synchronization of circadian rhythm from microbiota to hippocampal memory formation and circadian regulation through a Piezo2 initiated proton signaled manner through VGLUT3 allosteric transmission at a distance. Furthermore, this paper posits that these unaccounted ultrafast proton-based long-range oscillatory synchronizing axes may exist not only within the brain, but between the periphery and the brain, in an analogous way like in the case of this introduced microbiota-gut-brain axis. Finally, the irreversible Piezo2 channelopathy induced lost Piezo2 initiated prefrontal-hippocampal axis likely leads not only to Alzheimer’s disease, but the same irreversible microdamage induced lost Piezo2 initiated muscle spindle-hippocampal and cerebellum-hippocampal axes may lead to amyotrophic lateral sclerosis and Parkinson’s disease respectively.