# Oral Microbiota in Patients with Alzheimer's Disease: A Systematic Review
###### Abstract  
Oral microorganisms have been found in the cerebral milieu, suggesting the involvement of oral microbiota in the onset and course of Alzheimer's Disease (AD) through mechanisms such as amyloid-beta accumulation, tau phosphorylation and neuroinflammation. It is still uncertain whether and which oral bacteria are associated with AD. Therefore, the aim of this systematic review was to assess the current evidence for associations between oral microbiota and AD. A database search in Pubmed and Embase resulted in 623 hits. After removing duplicates, 437 papers remained. Of these, 13 papers passed the inclusion criteria and were included for quality/risk of bias assessment and data extraction. Analysis of these 13 studies revealed high heterogeneity in terms of sample size, age, study design and microbiological methods. Quality assessment using the MINORS criteria indicated reasonable to good quality across studies. As a result of the omission of two of the criteria, the quality results may have been biased. There is no conclusive evidence as to if and which oral microbiota are associated with AD since many conflicting results were reported. Although the overall quality of the studies was acceptable, the studies differed in study design and protocol. Further research is needed to clarify this association.  
Alzheimer's disease; oral microbiota; oral health; dementia +
Footnote †: journal: Medicalhealthcare burden [7]. The increasing prevalence of AD, coupled with the absence of targeted therapeutic strategies, underscores the critical need to unravel the underlying causes of the disease [4; 7; 9]. Among the myriad factors under investigation as potential causes or contributors to AD, oral health has emerged as a compelling area of interest [4; 7; 9]. Conditions such as gingivitis, periodontitis, caries and fungal infections are not merely confined to the mouth but may also have systemic implications [7]. For instance, bacteria from the mouth can enter the bloodstream and gastrointestinal tract and spread throughout the body [10]. It has been shown that periodontitis is linked to several systemic conditions such as cardiovascular diseases, diabetes and, recently, neurodegenerative diseases [11; 12].  
There is indeed some evidence of intricate relationships between oral health and the pathogenesis of AD, with a focus on the potential role of the oral microbiota [12]. Oral microbiota has been found in the cerebral milieu, suggesting their involvement in the onset and course of AD through mechanisms such as amyloid-beta accumulation, tau phosphorylation and neuroinflammation [13]. Suggested pathways for oral microbiota to enter the brain are via the bloodstream and blood-brain barrier (periodontitis), the nervus olfactorius (nasopharynx) and the nervus vagus (brain-gut axis) [14; 15]. The Understanding the gut-brain connection is crucial in the context of neurodegenerative diseases, as a similar mechanism may underlie the mouth-brain axis [14]. However, it remains unclear whether oral bacteria are indeed associated with the onset of AD.  
This systematic review aimed to provide an overview of the associations between oral microbiota (oral microbiome) and AD.