Increasing evidence suggests that the severe gum disease, periodontitis, may contribute to central nervous system disorders through chronic inflammation. However, its role in multiple sclerosis, a chronic autoimmune disease of the central nervous system, has been unclear. A research team has conducted a study with findings that suggest a potential association between the relative abundance of Fusobacterium nucleatum (F. nucleatum), a bacterium found in the mouth, and disease severity in multiple sclerosis (MS) patients.
Their research is published in the journal Scientific Reports on November 3, 2025.
Multiple sclerosis is a central inflammatory demyelinating disease that targets the myelin sheath, the protective layer that wraps around some nerve cells. While the specific cause of multiple sclerosis remains unknown, viral infections, smoking, vitamin deficiencies, and genetic predispositions are thought to be possible contributing factors.
The prevalence of multiple sclerosis has been steadily increasing in Japan since the 1980s. This rapid increase might be influenced by environmental changes. Scientists have extensively studied alterations in the gut microbiome related to this. Recent attention has expanded to include the possible role of oral microbiota, alongside gut microbiota, in central nervous system diseases.
Periodontal disease is a chronic bacterial infection that triggers persistent inflammation in periodontal tissues. It ultimately destroys the connective tissues and alveolar bone and result in tooth loss. Periodontal disease is common, with a global prevalence of 40 to 60 percent. Researchers know that it increases the risk of diseases like atherosclerosis, diabetes, and rheumatoid arthritis.
Exploring a potential 'oral–brain axis' in MS
In their study, the research team quantified the periodontal bacterial load in tongue coating samples collected from patients with central inflammatory demyelinating diseases like multiple sclerosis, neuromyelitis optica spectrum disorder (NMOSD), or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). High relative abundance was determined based on whether the proportion of a given bacterial species in their oral samples was in the top 25% of all patients studied (high) or in the bottom 75% (low).
They investigated the relationships between the periodontal bacterial load and clinical factors and the differential effects of various bacterial species.
The team aimed to determine whether specific periodontal pathogens in the oral cavity are associated with clinical severity in multiple sclerosis. "While the gut microbiome has been extensively investigated in multiple sclerosis, the potential involvement of the oral microbiome has remained largely unexplored. Because the oral cavity is a major source of chronic inflammation and represents a potentially modifiable factor, clarifying its relationship with multiple sclerosis severity is important for understanding disease mechanisms and developing new preventive strategies," said Masahiro Nakamori , an associate professor and lecturer at Hiroshima University Hospital .
Their findings show that multiple sclerosis patients with a higher relative abundance of the periodontal pathogen Fusobacterium nucleatum in tongue-coating samples showed significantly greater disability, as measured by the 10-point Expanded Disability Status Scale (EDSS).
"This association was not observed in neuromyelitis optica spectrum disorder or myelin oligodendrocyte glycoprotein antibody-associated disease, suggesting a potentially multiple sclerosis-specific 'oral–brain axis' through which oral inflammation may influence neuroinflammatory disease severity," said Hiroyuki Naito , an assistant professor at Hiroshima University Hospital.
A 'bridge bacterium'?
To rule out alternative explanations, the team tested a range of clinical factors alongside the bacterium. Even after adjusting for age, disease duration, number of attacks, and multiple sclerosis subtype, high levels of Fusobacterium nucleatum were associated with about tenfold higher odds of severe disability in multiple sclerosis patients.
The team noted that nearly two-thirds (61.5%) of multiple sclerosis patients with a high relative abundance of Fusobacterium nucleatum fell into the moderate-to-severe disability range (EDSS of 4 or greater), compared with roughly one-fifth (18.6%) of those with milder disease (EDSS below 4). No such association was observed in patients with neuromyelitis optica spectrum disorder or myelin oligodendrocyte glycoprotein antibody-associated disease. Multiple sclerosis patients with both Fusobacterium nucleatum and at least one other periodontal pathogen showed even higher disability.
"Fusobacterium nucleatum may act as a hidden 'bridge bacterium'—not only bridging bacterial communities in dental biofilms, but also potentially linking oral inflammation to neurological disability," said Nakamori.
Looking ahead, the team hopes to conduct larger, multi-center studies to validate the association between oral bacteria and multiple sclerosis severity. They plan to perform mechanistic analyses, including cytokine profiling and metagenomic sequencing, to understand how oral pathogens influence multiple sclerosis immunopathology. There is also a need to evaluate whether dental interventions—such as periodontal treatment or routine oral care—may modify disease activity or disability progression in multiple sclerosis. "Ultimately, we aim to clarify how the oral–gut–brain inflammatory axis contributes to multiple sclerosis pathophysiology and to explore whether oral health could serve as a novel target for disease modification," said Naito.
The research team also includes Megumi Toko, Tomoko Muguruma, Hidetada Yamada, Takamichi Sugimoto, Yu Yamazaki, Kazuhide Ochi, and Hirofumi Maruyama from Hiroshima University's Department of Clinical Neuroscience and Therapeutics and Hiromi Nishi and Hiroyuki Kawaguchi from the Department of General Dentistry , Hiroshima University Hospital.
