In recent years, researchers have established correlations between the state of the gut microbiome and development of neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease. The balance of microbial populations making up the gut microbiome shifts with age to promote greater inflammation and dysfunction throughout the body, though one can also argue that the aging of the immune system promotes both this gut dysbiosis and neurodegeneration. Assessing the degree to which specific mechanisms are responsible for specific conditions is challenging, given the complexity of aging and its consequences. Nonetheless, there is good reason to think that an aged gut microbiome is actively harmful. Here, researchers note that inappropriate migration of oral bacteria into the gut may also be involved in the aging of the gut microbiome and its impact on the aging of the brain.
The human microbiome is increasingly recognized for its crucial role in the development and progression of neurodegenerative diseases. While the gut-brain axis has been extensively studied, the contribution of the oral microbiome and gut-oral tropism in neurodegeneration has been largely overlooked. Cognitive impairment (CI) is common in neurodegenerative diseases and develops on a spectrum. In Parkinson's Disease (PD) patients, CI is one of the most common non-motor symptoms but its mechanistic development across the spectrum remains unclear, complicating early diagnosis of at-risk individuals.
Here, we generated 228 shotgun metagenomics samples of the gut and oral microbiomes across PD patients with mild cognitive impairment (PD-MCI) or dementia (PDD), and a healthy cohort, to study the role of gut and oral microbiomes on CI in PD. In addition to revealing compositional and functional signatures, the role of pathobionts, and dysregulated metabolic pathways of the oral and gut microbiome in PD-MCI and PDD, we also revealed the importance of oral-gut translocation in increasing abundance of virulence factors in PD and CI. The oral-gut virulence was further integrated with saliva metaproteomics and demonstrated their potential role in dysfunction of host immunity and brain endothelial cells.
Our findings highlight the significance of the oral-gut-brain axis and underscore its potential for discovering novel biomarkers for PD and CI.
Link: https://doi.org/10.1080/19490976.2025.2506843
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