# Dysbiotic shift in the oral microbiota of patients with Alzheimer's disease compared to their healthy life partners—a combinatorial approach and a paired study design

## TL;DR

This study finds a distinct oral microbiota pattern in Alzheimer's patients compared to their healthy partners, using a paired design and multiple sequencing methods.

## Contribution

First study using a paired design and combined sequencing to identify robust microbial features in Alzheimer's oral microbiota.

## Key findings

- A core dysbiosis was identified in Alzheimer's patients, excluding Porphyromonas gingivalis but including other oral pathogens.
- Host-compatible species like Prevotella melaninogenica were more common in healthy controls.
- The paired design and multi-omics approach increased statistical power for detecting disease-associated microbes.

## Abstract

The oral microbiota has been associated with Alzheimer's disease (AD). However, earlier studies provided conflicting results using varying sampling methods, sequencing techniques, and statistics, as well as independent subjects.

To robustly identify disease-associated microbial features, we recruited patients and their healthy life partners from the same households sharing a more similar microbiota compared to independent individuals increasing statistical power via paired design and combined three different sequencing methods – including metagenomics—and several bioinformatic pipelines. We recruited 26 AD-patients and their life partners. Salivary and supragingival samples were collected and a clinical examination of the mouth was performed.

Both groups showed comparable oral health. By focusing primarily on recurrently identified species across the different datasets we were able to identify a Core dysbiosis. This Core dysbiosis surprisingly spares the most central of oral diseases pathogens, namely Porphyromonas gingivalis. However, it includes numerous other species commonly associated with oral pathologies such as Prevotella nigrescens, Streptococcus anginosus, Dialister invisus, Anaeroglobus geminatus, Olsenella uli and Mogibacterium timidum. In contrast, more host-compatible species such as Prevotella melaninogenica or Streptococcus parasanguinis are identified in controls.

This is the first study using a combined sequencing approach and a paired study design to identify robust features of the oral microbiota of AD-patients. Although promising, the results should nevertheless be interpreted with caution, as the cross-sectional study design limits the possibilities of interpretation, and larger, longitudinal data are necessary for causal conclusions. However, this combined approach on multiple processing levels to identify intra-partnership differences still offers the possibility to better identify disease-associated microbial features potentially involved in AD-pathogenesis.

This study was prospectively registered at the German Clinical Trials Register (DRKS00023456) at the 30th of November 2020.

The online version contains supplementary material available at 10.1186/s13195-025-01941-1.