UCLA researchers in the School of Dentistry and section of Biosystems and Function have developed a novel diagnostic protocol to accurately categorize both the virome and microbiome of the oral-gut-brain axis for periodontitis, irritable bowel disease, and Alzheimer’s disease pathologies.
BACKGROUND: Humans are host to a large and diverse set of bacterial species which constitute our commensal microbiome, accounting for nearly half of all cells in the body. The disruption, or dysbiosis, of these communities is directly linked to certain pathologies such as periodontitis in the case of oral cavity dysbiosis or irritable bowel disease (IBD) in the gut. Alzheimer’s disease (AD), a cognitive disorder, has also been linked with other infectious diseases including periodontitis and the presence of relevant bacterial species. The precise underlying mechanisms of polymicrobial infections and their influence on these pathologies are poorly understood in part due to a limited understanding of the diverse microbiome in select areas. Beyond the human gut, characterization of the microbiomes of other organs is sparse, particularly in the oral cavity and brain. Accurate assessments of the various microbiomes present in the human body are vital for the control, prevention, and treatment of these diseases.
In addition to the microbiome, the virome plays an important role in health and disease. The ratio of virus-like particles (VLPs) to human cells far exceeds that of prokaryotes, but inventory of human viromes remains limited despite advances in metagenomic sequencing and viral cultivation technologies. Viruses have been implicated in periodontitis and IBD but a comprehensive analysis of how the virome changes and interacts with the microbiome has been absent. Current shotgun sequencing used for virome and microbiome assessment are hampered both by their inability to effectively enrich specifically for non-host DNA as well as their limited accessibility to certain tissues like the brain. Therefore, there is a need for a sensitive, high-coverage assay capable of simultaneously monitoring virome and microbiome changes.
INNOVATION: UCLA researchers led by Dr. Yvonne L. Kapila have developed a novel, high-coverage sequencing protocol that can accurately evaluate viromes and microbiota involved in the oral-gut-brain axis of human health and disease. These assays utilize a newly developed multiple displacement amplification (MDA)-based sequencing method and a targeted probe-based viral sequencing method to enrich samples for both viral and bacterial DNA from small sample volumes. Using this technology, the group has been able to identify the top 20 most abundant viral and bacterial species from saliva and stool samples collected from healthy patients compared to those with periodontitis and IBD. Samples collected from brain autopsy specimens and cerebrospinal fluid (CSF) have also been examined using this technology, revealing notable differences in viral populations between healthy and AD patients. Assays reveal differences in these top microbe levels between conditions of health and disease. The technology provides both a powerful diagnostic tool for monitoring virome and bacteriome changes in oral, gut, and brain diseases as well as a potential prognostic assay for early AD and other pathologies.
POTENTIAL APPLICATIONS:
- Periodontal disease diagnosis and prevention
- Improved early diagnosis of Alzheimer’s Disease
- IBD diagnosis and prevention
- Ability to monitor responses to treatments for periodontitis, IBD, and AD
ADVANTAGES:
- Improved enrichment for sample DNA from contaminant host DNA
- Provides metagenomic information on both virome and bacteriome from same sample
- Low sample volumes needed for accurate diagnosis
DEVELOPMENT-TO-DATE: The inventors have validated their results of identified bacterial/viral species from their assay using qPCR. Initial findings using the technology to distinguish virome and bacteriome differences in IBD and Periodontitis samples have also been verified with Simpson indices, an orthogonal diagnostic tool, calculated from the same samples. In addition, sequencing findings have also been validated in brains from healthy and AD patients using RNA scope in situ hybridization and in multiple different patient cohorts.
Related Papers (from the inventors only):
Zhao C et al. Nisin a probiotic bacteriocin mitigates brain microbiome dysbiosis and Alzheimer's disease-like neuroinflammation triggered by periodontal disease. J Neuroinflammation. 20(1):228 (2023)
Martinez A, Kuraji R, & Kapila YL. The human oral virome: Shedding light on the dark matter. Periodontol 2000. 87(1):282-298 (2021)
Gao L et al. Polymicrobial periodontal disease triggers a wide radius of effect and unique virome. NPJ Biofilms Microbiomes. 6(10) (2020)
Keywords: Virome, microbiome, bacteriome, Alzheimer’s Disease (AD), periodontitis, irritable bowel disease (IBD), oral disease, next-generation sequencing, metagenomics, neuroinflammation