Periodontal bacterial burden associated with disease severity in multiple sclerosis

Periodontal bacterial burden associated with disease severity in multiple sclerosis

There is increasing evidence that the serious gum disease periodontitis can contribute to central nervous system disorders through chronic inflammation. However, its role in multiple sclerosis, a chronic autoimmune disease of the central nervous system, is unclear. A research team has conducted a study with results suggesting a possible connection between the relative frequency of...Fusobacterium nucleatum(F. nucleatum), a bacterium found in the mouth, and the severity of disease in patients with multiple sclerosis (MS).

Your research will be published in the journalScientific reportson November 3, 2025.

Multiple sclerosis is a central inflammatory demyelinating disease that attacks the myelin sheath, the protective layer that covers some nerve cells. While the specific cause of multiple sclerosis is still unknown, viral infections, smoking, vitamin deficiencies and genetic predispositions are considered possible triggers.

The prevalence of multiple sclerosis has increased steadily in Japan since the 1980s. This rapid increase could be influenced by environmental changes. Scientists have studied the associated changes in the intestinal microbiome in detail. Recent attention has expanded to the potential role of oral microbiota alongside gut microbiota in central nervous system diseases.

Periodontitis is a chronic bacterial infection that causes persistent inflammation in periodontal tissue. It ultimately destroys the connective tissue and alveolar bone and leads to tooth loss. Periodontitis is a common disease with a global prevalence of 40 to 60 percent. Researchers know it increases the risk of diseases such as atherosclerosis, diabetes and rheumatoid arthritis.

Exploring a possible “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 such as 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 particular bacterial species in their oral samples was in the top 25% of all patients examined (high) or in the bottom 75% (low).

They examined the relationships between periodontal bacterial load and clinical factors, as well as the different effects of different bacterial species.

The team wanted to find out whether certain periodontal pathogens in the oral cavity are associated with the clinical severity of multiple sclerosis.

While the gut microbiome has been extensively studied in multiple sclerosis, the possible involvement of the oral microbiome remains largely unexplored. Because the oral cavity represents a major source of chronic inflammation and a potentially modifiable factor, clarifying its association with multiple sclerosis severity is important to understand disease mechanisms and develop new prevention strategies.”

Masahiro Nakamori, Associate Professor and Lecturer, Hiroshima University Hospital

Their results show that multiple sclerosis patients have a higher relative frequency of the periodontal pathogenFusobacterium nucleatumin tongue coating samples showed significantly greater disability as measured by the 10-item Expanded Disability Status Scale (EDSS).

"This association was not observed in neuromyelitis optica spectrum disorder or in myelin oligodendrocyte glycoprotein antibody-associated diseases, suggesting a potentially multiple sclerosis-specific 'oral-brain axis' through which oral inflammation may influence the severity of neuroinflammatory diseases," said Hiroyuki Naito, assistant professor at Hiroshima University Hospital.

A “bridge bacteria”?

To rule out alternative explanations, the team tested a number of clinical factors in addition to the bacterium. Even after taking into account age, duration of illness, number of attacks and the subtype of multiple sclerosis, the values ​​are highFusobacterium nucleatumwere associated with an approximately tenfold higher risk of severe disability in multiple sclerosis patients.

The team found that it affects nearly two-thirds (61.5%) of multiple sclerosis patients at a high relative frequencyFusobacterium nucleatumfell in the moderate to severe disability range (EDSS of 4 or higher), compared with approximately one-fifth (18.6%) of those with milder disease (EDSS less than 4). No such association was observed in patients with neuromyelitis optica spectrum disorder or myelin oligodendrocyte glycoprotein antibody-associated disease. Multiple sclerosis patients with bothFusobacterium nucleatumand at least one other periodontal pathogen showed even greater disability.

“Fusobacterium nucleatummay act as a hidden “bridge bacteria,” not only bridging bacterial communities in dental biofilms, but also potentially linking oral inflammation to neurological disability,” Nakamori said.

Looking forward, the team hopes to conduct larger, multicenter studies to validate the association between oral bacteria and multiple sclerosis severity. They plan to conduct mechanistic analyses, including cytokine profiling and metagenomic sequencing, to understand how oral pathogens influence the immunopathology of multiple sclerosis. There is also a need to investigate whether dental interventions – such as periodontal treatment or routine oral care – can influence disease activity or disability progression in multiple sclerosis. “Ultimately, we want to clarify how the mouth-gut-brain inflammatory axis contributes to the pathophysiology of multiple sclerosis and investigate whether oral health could serve as a new target for disease modification,” Naito said.

The research team also includes Megumi Toko, Tomoko Muguruma, Hidetada Yamada, Takamichi Sugimoto, Yu Yamazaki, Kazuhide Ochi and Hirofumi Maruyama from the Department of Clinical Neuroscience and Therapeutics at Hiroshima University, and Hiromi Nishi and Hiroyuki Kawaguchi from the Department of General Dentistry at Hiroshima University Hospital.

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