Analysis of Salivary Microbiome in Patients with Alzheimer’s Disease

Abstract

Recent studies found that poor oral hygiene was associated with increased risk of dementia, and the number of oral bacteria significantly increased in the brain tissues of patients with Alzheimer's disease (AD), suggesting that the oral microbiota may play an important role in the pathogenesis of AD. However, the actual composition of oral bacteria communities in patients with AD and whether these oral bacteria are associated with disease severity remain largely unknown. Also, the APOE 4 polymorphism is a strong risk factor for sporadic AD, and it would be pertinent to see if the bacterial flora was different in those patients who were APOE 4 positive. A total of 78 subjects were recruited in this study, including 39 patients with AD and 39 healthy controls. Saliva was collected from each subject. 16S ribosomal RNA (16S rRNA) sequencing was conducted to analyze the salivary microbiota, and Sanger sequencing was performed to analyze the APOE genotype. There was a significantly lower richness and diversity of saliva microbiota detected in AD patients than healthy controls. The relative abundance of Moraxella, Leptotrichia, and Sphaerochaeta in the saliva of AD patients greatly increased, whereas that of Rothia was significantly reduced. Compared with APOE 4 (-) patients, the level of Abiotrophia and Desulfomicrobium was comparatively abundant, while Actinobacillus and Actinomyces decreased significantly in patients carrying the APOE 4. No bacteria were found to be associated with the severity of AD. This is the first study to analyze the salivary microorganisms in patients with AD, and we discovered that the composition of salivary microbiome was altered in AD, providing further support for the role of the oral microbiome in AD development.

The Links Between the Gut Microbiome, Aging, Modern Lifestyle and Alzheimer's Disease

“…A nationwide, retrospective, matched-cohort study in Taiwan showed that patients with chronic periodontitis and gingivitis have a higher risk of developing dementia compared to those with healthy gums (Tzeng et al, 2016). Moreover, recent accumulating evidence has demonstrated a causal relationship between oral microbiome and AD (Paganini-Hill et al, 2012;Harding et al, 2017;Liu et al, 2019b;Panza et al, 2019;Olsen and Singhrao, 2020). For example, P. gingivalis, the most common periodontal bacteria causing periodontal disease, was capable of inducing accumulation of amyloidbeta plaques and neurofibrillary tangles following experimental oral infection in mice (Dominy et al, 2019).…”

“…In addition, there is data indicating the significant differences in quantity and quality of oral microbiome in AD patients compared to mentally healthy individuals of the same age. For example, Liu et al have demonstrated lower richness and diversity of salivary microbiome in patients with Alzheimer's disease compared to healthy controls (Liu et al, 2019b). The authors reported a relatively high level of Moraxella, Leptotrichia, and Sphaerochaeta and significantly decreased number of Rothia in the saliva of AD patients (Liu et al, 2019b).…”

“…For example, Liu et al have demonstrated lower richness and diversity of salivary microbiome in patients with Alzheimer's disease compared to healthy controls (Liu et al, 2019b). The authors reported a relatively high level of Moraxella, Leptotrichia, and Sphaerochaeta and significantly decreased number of Rothia in the saliva of AD patients (Liu et al, 2019b). However, these authors emphasize the limitations of the study due to the absence of many periodontal bacteria in saliva which exist within the subgingival niche or dental plaques (Filoche et al, 2009).…”

Analysis of oral microbiome in chronic periodontitis with Alzheimer’s disease: Pilot study

“…Interestingly, oral bacteria have been frequently observed in the AD brain tissue compared with normal controls suggesting possible roles of oral microbiome in pathogenesis of AD (18,19). Recently, salivary microbiome in AD patients showed reduced diversity compared with healthy controls (20). Oronasal cavity is close to brain and has associated with the brain via the trigeminal and olfactory nerves (21).…”

“…Thus, dysbiotic oral microbiome has been suggested to increase the infection of opportunistic pathogens in the brain of AD patients and further contribute to the development of AD (18,22). Few studies have been conducted to characterize the oral microbiome in AD (20). Moreover, there is no study that has focused on CP patients with AD.…”