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

Oct 18, 2024Journal of neuroinflammation

Periodontitis disrupts gut balance and worsens Alzheimer's symptoms in mice

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Abstract

exacerbates cognitive impairment and anxious behavior in (AD) mice after 8 weeks.

Periodontitis is associated with increased Aβ deposition and microglial overactivation in the brains of AD mice.
Alterations in composition and colon inflammation were observed in AD mice with periodontitis.
Fecal transplantation from periodontitis mice to antibiotic-treated AD mice resulted in worsened AD progression and disrupted intestinal homeostasis.
Intestinal barrier function impairment and elevated peripheral inflammation were noted in AD mice affected by periodontitis.
The findings suggest that periodontitis may disrupt intestinal homeostasis, contributing to AD progression through gut microbial dysbiosis and neuroinflammation.

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exacerbates (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/PS1(APP/PS1) mice. Behavioral tests and histological analyses of brain tissue were conducted after 8 weeks. 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. swe ΔE9

Key numbers

1.7×

Increased Risk of AD

Risk ratio comparing patients to healthy people.

8 of 16

Cognitive Impairment

Number of impaired mice out of the total tested.

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

Abstract

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