With ads everywhere for pro- or pre-biotic foods and supplements, most people are familiar with the gut microbiome—the trillions of bacteria, fungi, and viruses that colonize our digestive tract—and the idea that keeping our gut microbiome healthy improves our overall health. But other areas of our bodies harbor their own unique microbiomes as well, and researchers are now starting to explore the role these microbial ecosystems play in health and disease.
University of Iowa Health Care researchers have produced the most comprehensive genetic and metabolic analysis to date of the oral microbiome associated with multiple sclerosis (MS), a progressive autoimmune disease that damages nerves in the brain and spinal cord. They found that people with MS have a distinct (dysbiotic) oral microbiome compared to healthy individuals.
"While the gut microbiome has long been linked to MS, the oral microbiome, our mouth's rich microbial ecosystem, has received far less attention, even though it's the second most diverse microbiome in the human body and has been linked with other neurological diseases, like Alzheimer's disease, and inflammatory diseases, like rheumatoid arthritis," says Ashutosh Mangalam, PhD, UI professor of pathology and senior author of the new study, which recently published in the journal npj Bioflims and Microbiomes .
"Your mouth may reveal more about your overall health than you think," he adds. "Our study shows that people with MS have measurable differences in the bacteria and metabolites found in their saliva. And this isn't just about losing a few good bacteria; it suggests a there is a breakdown of the oral ecosystem in people with MS."
While there are treatments that can slow down MS, which causes muscle weakness, balance issues, and problems with vision and thinking, there is currently no cure for MS.
The knowledge gleaned from the new study could eventually help doctors develop simple saliva-based tests to detect or monitor MS and may open the door to new classes of MS treatments that replace or restore healthy bacteria.
MS characterized by loss of good bacteria, enrichment of bad bacteria
Mangalam and his team used shotgun metagenomic sequencing and untargeted metabolomics to study how changes to the entire community of bacteria in the mouth and small molecules (metabolites) these organisms produce might influence MS.
They analyzed saliva from 50 people with relapsing–remitting MS (RRMS), the most common form of MS, and from 50 healthy controls. Compared to healthy people, individuals with MS had a disrupted oral microbiome. This imbalance was primarily characterized by a loss of beneficial "early colonizer" bacteria, such as Streptococcus and Actinomyces that are the building blocks of a healthy oral community, and an increase in bacteria with the potential to cause disease, including Fusobacterium nucleatum, Porphyromonas gingivalis, and several Prevotella species.
The metabolic profile of the saliva, a measure of the small molecules (metabolites) produced by both patient and bacteria, was also distinct. People with MS had reduced levels of a protective metabolite called hypotaurine, which is involved in antioxidant defense and nerve health. The study suggests that the decreased hypotaurine levels are likely linked to the altered bacteria in the MS oral microbiome.
Together, these findings suggest that oral microbial and metabolic changes may contribute to inflammation and disease processes in MS.
The researchers also developed a novel machine-learning approach called topic modeling that allowed them to identify groups of bacteria that coexist as communities. This analysis uncovered microbial networks that are unique to healthy individuals and showed that five microbial communities were significantly lost in MS patients. This loss suggests a fundamental breakdown in the cooperative microbial network that maintains oral health.
"This multi-omics approach revealed how bacterial composition, function, and metabolite profiles are interconnected, highlighting specific bacterial taxa and metabolic signatures that may shape inflammation and immune dysregulation in MS," Mangalam says. "These findings provide one of the most detailed views to date of the relationship between oral microbes, bacterial function, and host metabolism in MS. The results expand our understanding of MS beyond the gut and brain and highlight the mouth as another important site of immune-microbial interaction."
Oral microbiome offers opportunities for new diagnostics, therapies
The new findings could lead to better ways to diagnose, monitor, and even treat MS.
Because saliva collection is simple and non-invasive, the oral microbiome and metabolome could become valuable biomarkers for monitoring disease activity or response to treatment. For example, microbiome profiling could be used to create a diagnostic signature for MS, and measuring hypotaurine levels in saliva could be simple, non-invasive biomarker to aid in diagnosis or disease monitoring.
In addition, since the oral microbiome is easier to access and manipulate than the gut microbiome, the findings could open the door to a new class of MS treatments that replace or restore healthy bacteria to improve disease management and patient outcomes.
The multidisciplinary research team included scientists from the UI Carver College of Medicine, College of Dentistry, College of Public Health, College of Nursing, and Holden Comprehensive Cancer Center. In addition to Mangalam, the team included Rachel Fitzjerrells, lead author and a graduate student in Mangalam's lab, Leeann Aguilar Meza, Meeta Yadav, Heena Olalde, Mishelle Paullus, Jemmie Hoang, Catherine Cherwin, Tracey Cho, Grant Brown, and Sukirth M. Ganesan.
The research was funded in part by grants from the National Institute of Health.
