Arginine helps modulate dental biofilm virulence

Iveta Ramonaite, Dental Tribune International

Thu. 5 February 2026

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AARHUS, Denmark: Recent research increasingly highlights the importance of ecology-based strategies in caries prevention. A new human clinical study has provided evidence that arginine, a naturally occurring amino acid, can influence dental biofilm development in a way that reduces its harmful potential and may help protect against caries. Conducted in patients with active caries, the study demonstrates that arginine alters biofilm acidity, structure and microbial composition in a manner that preserves biofilm ecology.

The split-mouth study included ten patients who wore custom intra-oral splints for four days to allow in situ biofilm growth. The biofilms underwent three daily cycles of splint placement in a sucrose solution for 5 minutes and then in an arginine or placebo solution for 30 minutes. This approach enabled the researchers to directly compare arginine-treated and untreated biofilms under clinically relevant conditions.

Professor of cariology Dr Sebastian Schlafer believes that understanding how arginine affects the interplay between the pH, microbial composition and structure of the dental biofilm matrix could help improve caries treatment strategies. (Image: Prof. Sebastian Schlafer)

Changes in pH levels and biofilm matrix architecture

Using a pH-sensitive dye, the researchers measured micro-scale pH changes within the participants’ biofilms following the sucrose challenge. They found that biofilms exposed to arginine showed significantly higher pH levels 10 and 35 minutes after sucrose exposure compared with placebo-treated biofilms.

The study also examined the extracellular matrix of the biofilms, focusing on carbohydrate components that contribute to virulence. After analysing the findings, the researchers observed that arginine treatment led to an overall reduction in fucose-containing matrix carbohydrates and altered the spatial distribution of galactose-containing matrix carbohydrates. Galactose-containing material decreased at the biofilm base and increased at the surface. These structural changes could reduce the formation of strongly acidic micro-niches within plaque and may help promote a less cariogenic biofilm environment.

Microbiome modulation rather than bacterial eradication

The researchers then assessed the microbial biofilm composition. They found that both arginine- and placebo-treated biofilms were dominated by Streptococcus and Veillonella species. However, arginine significantly reduced the proportion of acid-producing bacteria of the S. mitis and S. oralis group and slightly increased the relative abundance of bacteria capable of metabolising arginine into alkali. Together, these shifts may help to explain the improved pH control observed in arginine-treated biofilms.

Senior author Dr Sebastian Schlafer, professor in the Department of Dentistry and Oral Health at Aarhus University, explained arginine’s broader clinical relevance. He told Dental Tribune International: “Most currently used adjuncts to self-performed oral hygiene rely on antimicrobial agents. This is a rather unspecific strategy, since these agents do not distinguish between beneficial and harmful bacteria.”

“Our findings support the idea that caries can be effectively counteracted using a non-biocidal, ecology-based strategy.”—Dr Yumi Chokyu Del Rey

“Arginine represents a more ecological approach: instead of aiming to eradicate microorganisms, it modulates the oral microbiota in a favourable direction. We already know that arginine stimulates the growth and activity of alkali-producing bacteria and counteracts the activity of cariogenic bacteria. However, there is still very limited knowledge about how arginine affects the interplay between pH, microbial composition and the structure of the dental biofilm matrix. By understanding these mechanisms in more detail, we can better explain why some patients benefit more from arginine-based therapies than others and, in the long term, potentially optimise clinical treatment strategies,” he explained.

Clinical relevance and future directions

Dr Yumi Chokyu Del Rey says that the recent study on arginine that she led offers a non-biocidal, ecology-based strategy to prevent dental caries. (Image: Dr Yumi Chokyu Del Rey)

According to lead author Dr Yumi Chokyu Del Rey, postdoctoral researcher at Aarhus University, the study fills an important gap between laboratory findings and clinical evidence. She told Dental Tribune International: “This study is, to our knowledge, the first to demonstrate the combined effects of arginine on biofilm pH, microbial composition and matrix architecture in dental biofilms. We observed a positive effect of arginine on biofilm pH, even though it was applied in a group of patients with an average of around ten active lesions per person. In addition, we detected an increase in arginine-metabolising organisms and an overall reduction in the production of carbohydrate-based matrix components, which may indicate the formation of less harmful biofilms. Interestingly, however, we did not find a clear correlation between these microbiological or structural changes and the individual pH response to arginine treatment.”

The findings support the use of arginine as a non-antimicrobial adjunct in caries prevention, targeting biofilm ecology rather than indiscriminate bacterial killing. “Our findings support the idea that caries can be effectively counteracted using a non-biocidal, ecology-based strategy such as arginine supplementation in oral care products. At the same time, our results highlight that individual responses to arginine vary and are not yet fully understood,” Dr Del Rey concluded.

Overall, the study provides compelling clinical evidence that arginine can reduce the virulence of dental biofilms through multiple complementary mechanisms—attenuating plaque acidification, reshaping biofilm structure and favourably modulating the oral microbiome. Further research is needed to identify the factors that determine who benefits most from this type of treatment and how it can be optimally applied in clinical practice.

The study, titled “Arginine modulates the pH, microbial composition, and matrix architecture of biofilms from caries-active patients”, was published online on 20 November 2025 in the International Journal of Oral Science.