Multiple sclerosis (MS) is a chronic neuroinflammatory disease affecting nearly three million people worldwide. While the gut microbiome has been widely studied in MS, the role of the oral microbiome has remained largely unexplored. Two recent studies from Ashutosh Mangalam, PhD’s laboratory now provide converging evidence that oral microbial imbalance is closely linked to immune activation and metabolic disruption in people with relapsing-remitting MS (RRMS), highlighting oral health as an underappreciated contributor to MS pathobiology.

This work reflects a strong interdisciplinary collaboration between immunology, oral health, neurology, and nursing. Dr. Mangalam partnered with Sukirth Ganesan, DDS, PhD, MPH, Associate Professor of Periodontics and an oral health expert from the College of Dentistry whose expertise was central to interpreting disease-relevant microbial patterns. Patient recruitment and clinical coordination were led by the Neurology research team at University of Iowa Health Care, including clinicians, nurses, and study coordinators working directly with MS participants. Recruitment of healthy control participants was coordinated by Catherine Cherwin, PhD, RN from the College of Nursing.

In the most recent study, the team combined shotgun metagenomics with untargeted salivary metabolomics to generate a high-resolution map of oral microbial and metabolic changes in RRMS. The analysis revealed depletion of beneficial early colonizers such as Streptococcus and Actinomyces, alongside enrichment of inflammatory pathobionts including Fusobacterium nucleatum, Porphyromonas gingivalis, and several Prevotella species. Using machine-learning-based community analysis, the researchers further showed that coordinated, health-associated microbial communities were lost in MS patients.

Functional profiling demonstrated that oral bacteria in MS exhibit altered metabolic capacity, with reduced detoxification and redox pathways and increased pathways linked to immunostimulatory bacterial components. Metabolomic analysis identified hypotaurine, a molecule linked to neuroprotection and myelin biology, as significantly reduced in MS patients and one of the strongest features distinguishing patients from healthy controls. In addition, coordinated relationships between oral microbes and metabolites were markedly disrupted in MS, indicating breakdown of normal microbial ecosystem function.

These findings build on a complementary study from the same team using 16S rRNA sequencing and salivary cytokine profiling. That work demonstrated enrichment of inflammatory taxa such as Campylobacter and Porphyromonas, increased lipopolysaccharide biosynthesis capacity, and elevated proinflammatory cytokines including IFN-γ and IL-6 in RRMS patients. Together, the studies establish a unified framework linking oral dysbiosis, functional microbial shifts, metabolic disruption, and immune activation in MS.

Collectively, this body of work highlights the oral cavity as a clinically accessible window into systemic immune dysregulation and supports oral health as a promising target for biomarker development, disease monitoring, and future microbiome-based therapeutic strategies in MS.

The shotgun metagenomics and metabolomics study was published in NPJ Biofilms and Microbiomes, while the complementary 16S and cytokine profiling study was published in Annals of Clinical and Translational Neurology.