Plasmon-activated water as a therapeutic strategy in Alzheimer's disease by altering gut microbiota

Gut microbiota (GM) are involved in the pathophysiology of Alzheimer's disease (AD) and might correlate to the machinery of the gut-brain axis. Alteration of the GM profiles becomes a potential therapy strategy in AD. Here, we found that plasmon-activated water (PAW) therapy altered GM profile and reduced AD symptoms in APPswe/PS1dE9 transgenic mice (AD mice). GM profile showed the difference between AD and WT mice. PAW therapy in AD mice altered GM profile and fecal microbiota transplantation (FMT) reproduced GM profile in AD mice. PAW therapy and FMT in AD mice reduced cognitive decline and amyloid accumulation by novel object recognition (NOR) test and amyloid PET imaging. Immunofluorescent staining and western blot analysis of β-amyloid (Aβ) and phosphorylated (p)-tau in the brain of AD mice were reduced in PAW therapy and FMT. The inflammatory markers, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α and pro-inflammatory indicator of arginase-1/CD86 ratio were also reduced. Furthermore, immunohistochemistry (IHC) analysis of occludin and claudin-5 in the intestine and AXL in the brain were increased to correlate with the abundant GM in PAW therapy and FMT. Our results showed the machinery of gut-brain axis, and PAW might be a potential therapeutic strategy in AD.