Project Team
Melanie Walker, MD, Clinical Professor of Neurological Surgery, University of Washington
Tim Henrich MD, Professor of Medicine, University of California San Francisco
Michael VanElzakker, PhD, Assistant Professor of Psychiatry, Massachusetts General Hospital/Harvard Medical School
Project Summary:
Dr. Michael VanElzakker helps the project team select sections of the vagus nerve to study.
To use unbiased next generation metagenomic sequencing to characterize the healthy vagus nerve microbiome/virome. Vagus nerve tissue samples analyzed for the project – including samples containing nerve ganglia bodies – are being collected during surgery.
Project Background:
The vagus nerve is the longest cranial nerve in the body, extending from the brainstem down through the neck and into the chest and abdomen, where it interfaces with key organs including the heart, lungs, and gastrointestinal tract. As a major component of the parasympathetic nervous system, it plays a central role in regulating autonomic functions such as heart rate, digestion, respiratory rate, and immune modulation.
Increasing research shows that the vagus nerve can become directly infected. For example, one recent Alzheimer’s disease study found Cytomegalovirus in tissue collected from the vagus nerve. The findings suggest that the vagus nerve may serve as a conduct for the virus to travel from the gut into the brain, where it can drive Alzheimer’s-associated pathology. Another team identified SARS-CoV-2 RNA directly in vagus nerve tissue samples collected from acute COVID-19 patients.
The vagus nerve is a prime site of potential infection by neurotrophic pathogens
Indeed, because the vagus nerve is such a prominent route of connection between the body and the brain, a growing number of scientists hypothesize that dozens of bacteria, viruses, or other organisms may traffic the nerve on a regular basis. This could positions the vagus nerve as a potential “superhighway” between the body and the brain for a range of infectious agents. However, the degree to which pathogens/organisms persist in the vagus nerve is dramatically understudied. This is because it is very hard to obtain vagus nerve samples – which cannot be collected via standard tissue biopsy procedures – to analyze for the presence of viruses, bacteria, or other microbes.
This project fills that gap by – for the first time in the world – collecting different segments/nerve bodies of the vagus nerve from trauma victims undergoing surgery. Samples are being collected during these surgeries by neurosurgeon Dr. Melanie Walker and team at University of Washington. Priority is placed on obtaining cell bodies from the ganglia and paraganglia of the vagus nerve.
Samples are immediately preserved and shipped to University of California San Francisco for unbiased metagenomic sequencing analysis. The sequencing can identify any viral, bacterial, fungal or other organism in the samples. The results will determine if vagus nerve tissue collected from healthy individuals harbors a microbiome/virome, and the central pathogens/organisms identified. Identified organisms may be pathogens whose ability to persist in and potentially travel the vagus nerve could contribute to Alzheimer’s disease, long COVID or other conditions involving persistent infections that can reach the brain.