Intestinal homeostasis disrupted by Periodontitis exacerbates Alzheimer's Disease in APP/PS1 mice.

Autor: Qian X; Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, P.R. China.; Institute of Stomatology & Laboratory of Oral Tissue Engineering, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, 350002, P.R. China., Lin X; Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, P.R. China.; Institute of Stomatology & Laboratory of Oral Tissue Engineering, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, 350002, P.R. China., Hu W; Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, P.R. China.; Institute of Stomatology & Laboratory of Oral Tissue Engineering, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, 350002, P.R. China., Zhang L; Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, P.R. China.; Institute of Stomatology & Laboratory of Oral Tissue Engineering, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, 350002, P.R. China., Chen W; Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, P.R. China.; Institute of Stomatology & Laboratory of Oral Tissue Engineering, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, 350002, P.R. China., Zhang S; Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, Jiangsu, 210008, P.R. China., Ge S; School and Hospital of Stomatology, Zunyi Medical University, Zunyi, Guizhou, 563003, P.R. China., Xu X; Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, P.R. China. xiongchengxu@fjmu.edu.cn.; Institute of Stomatology & Laboratory of Oral Tissue Engineering, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, 350002, P.R. China. xiongchengxu@fjmu.edu.cn., Luo K; Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, P.R. China. luokai39@163.com.; Institute of Stomatology & Laboratory of Oral Tissue Engineering, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, 350002, P.R. China. luokai39@163.com.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2024 Oct 18; Vol. 21 (1), pp. 263. Date of Electronic Publication: 2024 Oct 18.
DOI: 10.1186/s12974-024-03256-8
Abstrakt: Periodontitis exacerbates Alzheimer's disease (AD) through multiple pathways. Both periodontitis and AD are intricately correlated to intestinal homeostasis, yet there is still a lack of direct evidence regarding whether periodontitis can regulate the progression of AD by modulating intestinal homeostasis. The current study induced experimental periodontitis in AD mice by bilaterally ligating the maxillary second molars with silk and administering Pg-LPS injections in APP swe /PS1 ΔE9 (APP/PS1) mice. Behavioral tests and histological analyses of brain tissue were conducted after 8 weeks. Gut microbiota was analyzed and colon tissue were also evaluated. Then, fecal microbiota from mice with periodontitis was transplanted into antibiotic-treated mice to confirm the effects of periodontitis on AD and the potential mechanism was explored. The results indicated periodontitis exacerbated cognitive impairment and anxious behaviour in APP/PS1 mice, with increased Aβ deposition, microglial overactivation and neuroinflammation in brain. Moreover, the intestinal homeostasis of AD mice was altered by periodontitis, including affecting gut microbiota composition, causing colon inflammation and destroyed intestinal epithelial barrier. Furthermore, AD mice that underwent fecal transplantation from mice with periodontitis exhibited worsened AD progression and disrupted intestinal homeostasis. It also impaired intestinal barrier function, elevated peripheral inflammation, damaged blood-brain barrier (BBB) and caused neuroinflammation and synapses impairment. Taken together, the current study demonstrated that periodontitis could disrupt intestinal homeostasis to exacerbate AD progression potential via causing gut microbial dysbiosis, intestinal inflammation and intestinal barrier impairment to induce peripheral inflammation and damage BBB, ultimately leading to neuroinflammation and synapse impairment. It underscores the importance of maintaining both periodontal health and intestinal homeostasis to reduce the risk of AD.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje