Research Paper|Volume 15, Issue 9|pp 3715—3737

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

Chia-Hsiung Cheng¹, Yu-Chuan Liu^1,², Yu-Chen S.H. Yang³, Kun-Ju Lin^4,⁵, Dean Wu^6,^7,⁸, Yun-Ru Liu³, Chun-Chao Chang^9,^10,¹¹, Chien-Tai Hong^6,^7,¹², Chaur-Jong Hu^6,^7,^12,¹³

¹Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
²Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei 11031, Taiwan
³Joint Biobank, Office of Human Research, Taipei Medical University, Taipei 11031, Taiwan
⁴Department of Nuclear Medicine and Molecular Imaging Center, Linkou Chang Gung Memorial Hospital, Taoyuan City 33302, Taiwan
⁵Healthy Aging Research Center and Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan
⁶Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
⁷Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
⁸Sleep Center, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
⁹Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 11031, Taiwan
¹⁰Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
¹¹TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei 11031, Taiwan
¹²Department of Neurology and Dementia Center, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
¹³PhD program of Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan

* Equal contribution

Received: January 19, 2023Accepted: April 22, 2023Published: May 8, 2023

https://doi.org/10.18632/aging.204706

Copyright: © 2023 Cheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.