Disease- and stage-specific alterations of the oral and fecal microbiota in Alzheimer's disease

Microbial communities in the intestinal tract are suggested to impact the ethiopathogenesis of Alzheimer's disease (AD). The human microbiome might modulate neuroinflammatory processes and contribute to neurodegeneration in AD. However, the microbial compositions in patients with AD at different stages of the disease are still not fully characterized. We used 16S rRNA analyses to investigate the oral and fecal microbiota in patients with AD and mild cognitive impairment (MCI; n = 84), at-risk individuals (APOE4 carriers; n = 17), and healthy controls (n = 50) and investigated the relationship of microbial communities and disease-specific markers via multivariate- and network-based approaches. We found a slightly decreased diversity in the fecal microbiota of patients with AD (average Chao1 diversity for AD = 212 [SD = 66]; for controls = 215 [SD = 55]) and identified differences in bacterial abundances including Bacteroidetes, Ruminococcus, Sutterella, and Porphyromonadaceae. The diversity in the oral microbiota was increased in patients with AD and at-risk individuals (average Chao1 diversity for AD = 174 [SD = 60], for at-risk group = 195 [SD = 49]). Gram-negative proinflammatory bacteria including Haemophilus, Neisseria, Actinobacillus, and Porphyromonas were dominant oral bacteria in patients with AD and MCI and the abundance correlated with the cerebrospinal fluid biomarker. Taken together, we observed a strong shift in the fecal and the oral communities of patients with AD already prominent in prodromal and, in case of the oral microbiota, in at-risk stages. This indicates stage-dependent alterations in oral and fecal microbiota in AD which may contribute to the pathogenesis via a facilitated intestinal and systemic inflammation leading to neuroinflammation and neurodegeneration.