Patients with relapsing–remitting multiple sclerosis showed distinct oral microbial profiles and reduced salivary hypotaurine, suggesting possible diagnostic biomarkers. Researchers found a reduction in common Gram-positive species, including Streptococcus and Actinomyces, and an increase in Gram-negative bacteria such as Prevotella, Fusobacterium nucleatum, and Porphyromonas gingivalis.
Microbial diversity was lower in patients with relapsing–remitting multiple sclerosis (RRMS), while overall community composition differed significantly between patients and controls. In total, 102 microbial species varied in abundance, including 96 bacterial, 5 viral, and 1 fungal species. Most bacterial differences involved loss of early oral colonizers and enrichment of Gram-negative taxa.
Metabolomic analysis showed reduced levels of five salivary metabolites in patients with RRMS, including hypotaurine, fucose, and lauryl sulfate, and elevated levels of nine metabolites, including ribose-1-phosphate, guanosine, and nicotinamide. A random forest model distinguished RRMS from control samples with moderate accuracy, reinforcing consistent metabolite differences between groups. The study reported a 25% out-of-bag error rate for the random forest model, with classification accuracy of 67% for controls and 89% for patients with RRMS, indicating a consistent though imperfect predictive signal. Additionally, an orthogonal partial least squares discriminant analysis (OPLS-DA) model demonstrated good separation (R² = 0.91, Q² = 0.46), confirming that metabolomic profiles could differentiate the groups.
Functional pathway analysis showed reduced activity in the Superoxide Radicals Degradation and Molybdenum Cofactor Synthesis pathways, and increased activity in dTDP-β-L-rhamnose biosynthesis. These metabolic changes corresponded with the decrease in hypotaurine, a compound involved in taurine metabolism and oxidative balance. In healthy controls, hypotaurine positively correlated with Streptococcus and Actinomyces species, relationships that were absent in patients with RRMS, suggesting disrupted microbiome–metabolite interactions. Age, sex, smoking status, and use of disease-modifying therapy did not significantly affect diversity or metabolite outcomes.
“Our analyses consistently highlight a link between reduced hypotaurine levels and RRMS, suggesting that salivary hypotaurine may serve as both a novel therapeutic target and a potential biomarker for RRMS,” said senior author Ashutosh K. Mangalam, PhD, professor at the University of Iowa Carver College of Medicine, and colleagues.
The study used a cross-sectional case–control design with 50 adults with RRMS and 50 age-matched healthy controls. After quality control, 48 RRMS and 49 control samples were analyzed. Researchers performed shotgun metagenomic sequencing of oral swabs and untargeted salivary metabolomic profiling. Microbial diversity was evaluated using alpha and beta diversity measures, while compositional and functional analyses identified key differences between groups. Metabolomic profiling was conducted with liquid chromatography–mass spectrometry, and statistical testing determined significant variations. Correlation networks linked specific microbial species to metabolites, and a random forest model assessed classification accuracy.
The researchers noted several limitations. The study lacked dental or periodontal assessments, limiting evaluation of gum disease as a potential confounder. The single-center design may restrict generalizability, and the cross-sectional nature prevents establishing causality. The modest sample size also limited detection of smaller subgroup differences. Data supporting these findings are publicly available, with raw sequences deposited in the NCBI Sequence Read Archive (accession PRJNA1090491) and analytical code accessible through the researchers’ GitHub repository.
The researchers stated that the observed oral microbial and metabolic differences could reflect broader immune or metabolic dysregulation associated with multiple sclerosis. They emphasized that identifying consistent microbial and metabolite signatures may help develop future noninvasive biomarkers for disease monitoring. However, the findings remain preliminary and require validation in larger, longitudinal studies to determine causality and clinical relevance.
This research was supported by grants from the National Institutes of Health, the U.S. Department of Veterans Affairs, and institutional funding from the University of Iowa Carver College of Medicine. One author is listed on a patent related to Prevotella histicola for autoimmune disease, but no products or funds from that patent were used in this study.
Source: npj biofilms and microbioms
