Microbial communities in the intestinal tract have been suggested to impact the ethiopathogenesis of Alzheimer ′s disease (AD). The human microbiome might modulate neuroinflammatory processes and thus contribute to neurodegeneration in AD. However, the microbial compositions in AD patients 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), a cohort of at-risk individuals (APOE4 carriers) and healthy controls, and investigated the relationship of microbial communities and disease specific markers. We found a slightly decreased diversity in the fecal microbiota of AD patients and identified differences in bacterial abundances including Bacteroidetes, Ruminococcus, Sutterella, Porphyromonadaceae. The diversity in the oral microbiota was increased in AD patients and at-risk individuals. Gram-negative pro-inflammatory bacteria including Haemophilus, Neisseria, Actinobacillus and Porphyromonas were dominant oral bacteria in AD and MCI patients and the abundance correlated with the cerebrospinal fluid (CSF) 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.

Authors received institutional support by the German Research Foundation and by the Else Kröner-Fresenius Stiftung for the Interdisciplinary Else Kröner-Research College Kiel (The Role of the Gut-Brain-Axis in Neuroinflammation and Neurodegeneration) and the German Research Foundation for the Clinician Scientist Program in Evolutionary Medicine (CSEM).

Authors received institutional support by the German Research Foundation and by the Else Kröner-Fresenius Stiftung for the Interdisciplinary Else Kröner-Research College Kiel (The Role of the Gut-Brain-Axis in Neuroinflammation and Neurodegeneration) and the German Research Foundation for the Clinician Scientist Program in Evolutionary Medicine (CSEM).

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