The Oral Microbiome Is Site-Specific, and That Matters
Researchers have examined the human oral microbiome and discovered tremendous variability in bacterial subpopulations living in certain areas of the mouth. In many cases, the team was able to identify a handful of genes that might explain a particular bacterial group's habitat specificity.
Bacteria are not spread evenly through the mouth. A 2020 study led by researchers at Harvard found that even within a single bacterial species, different genetic groups prefer different places, such as the tongue or the inside of the cheek. The mouth behaves less like one ecosystem and more like a set of neighboring habitats, which helps explain why a single product rarely changes oral bacteria the way its label suggests.
What did the researchers do?
The team combined two kinds of data. The first was the genomes of bacteria that had been grown in labs. The second was genetic material collected directly from people's mouths by the Human Microbiome Project. Matching the two, an approach called metapangenomics, let them see which versions of a species actually live at each site and which genes they carry.
They looked at three sites: the top of the tongue, the inside of the cheek and plaque above the gumline. They focused on two common groups of mouth bacteria, Haemophilus parainfluenzae and the genus Rothia.
What did they find?
Haemophilus parainfluenzae split into three distinct genetic subgroups. Each was more common at some sites than others. The subgroup that favored the tongue carried a specific set of genes linked to energy metabolism, which may help it live there.
Rothia species mostly lived where expected. Rothia mucilaginosa was found mainly on the tongue, but the team also found a hidden population of it living on the inside of the cheek.
Lab strains did not fully represent the wild populations. Some genes found in lab-grown strains were rare or absent in the bacteria living in real mouths.
What are the limits?
This study used existing samples from healthy volunteers and looked at only two groups of bacteria and three sites. It describes where bacteria live and suggests how they adapt. It does not test any treatment or show how these differences affect cavities or gum disease.
Why does this matter for oral health?
The findings fit what dentists see every day. Plaque along the gumline, the coating on the tongue and the lining of the cheeks are different environments, and problems often start in one place before another. A few practical points follow:
Probiotic products are unlikely to work well unless the bacteria are suited to the site they are meant to colonize.
Research based only on lab strains can miss how bacteria behave in a real mouth.
Basic care still reaches every site. Brushing the teeth and gumline, cleaning between teeth and cleaning the tongue each disturb a different community.
Studies like this do not change treatment today, but they help researchers design more targeted ways to manage oral disease in the future. For daily care, see our home care instructions and how to brush correctly. A dental examination looks at all of these sites together.
Sources
Utter DR, Borisy GG, Eren AM, Cavanaugh CM, Mark Welch JL. Metapangenomics of the oral microbiome provides insights into habitat adaptation and cultivar diversity. Genome Biol. 2020;21(1):293. doi:10.1186/s13059-020-02200-2. Retrieved via PubMed.
About the author. CJ Henley, DMD, is a general dentist in Jacksonville whose practice focuses on cosmetic and restorative dentistry, dental implants and dental care around head and neck cancer. Meet Dr. Henley.
CJ Henley, DMD, PA · 3675 Hendricks Avenue, Jacksonville, FL 32207 · 904-398-1549
Updated October 2026.
Can a Drug Regrow Lost Teeth? Where the Research Stands
Scientists report that an antibody for one gene -- uterine sensitization associated gene-1 or USAG-1 -- can stimulate tooth growth in mice suffering from tooth agenesis.
Not yet. A 2021 study from Kyoto University and the University of Fukui showed that an antibody blocking a protein called USAG-1 could grow new teeth in mice and ferrets born with missing teeth. A first safety study in people began in Japan in late 2024, but no tooth regrowth drug is approved anywhere, and the first intended patients are children born without several teeth, not adults who have lost teeth.
What question did the 2021 study ask?
Tooth development depends on two signaling systems, BMP (bone morphogenetic protein) and Wnt. They also control growth throughout the body, so drugs that act on them directly could have wide side effects. USAG-1 is a protein that dampens both signals. Mice that lack USAG-1 grow extra teeth. The researchers asked whether blocking USAG-1 could restore teeth in animals born without some of them, a condition called congenital tooth agenesis.
What did they find?
In several mouse models of inherited tooth agenesis, removing the USAG-1 gene or giving an antibody against USAG-1 allowed missing teeth to form.
Some antibodies blocked USAG-1's effect on both BMP and Wnt. Those harmed the animals' growth and survival.
One antibody blocked only the interaction between USAG-1 and BMP. It was the useful one. According to the researchers, a single dose was enough to grow a whole tooth.
The approach also worked in ferrets, which, like people, have baby teeth followed by adult teeth.
The likely mechanism is that the antibody rescues tooth buds that start to form but normally stop developing.
What has happened since?
The research group and a company spun out of the university, Toregem BioPharma, developed a humanized version of the antibody called TRG035. In late 2024, a Phase 1 study began at Kyoto University Hospital. It is a randomized, placebo-controlled study in about 30 healthy adult men, testing a single intravenous dose at increasing strengths. A Phase 1 study looks at safety and how the body handles a drug. It is not designed to show whether new teeth grow.
The developers have said the next step is a study in children with congenital absence of multiple teeth. Whether the approach could ever help adults who lost teeth to decay, gum disease or injury is a separate, longer-term question.
What are the limits?
The strong results so far are in animals.
Phase 1 tests safety in a small group. Larger trials are needed to show that a tooth actually forms in people, in the right place, with a normal shape and root.
Approval, if it comes, would be for a defined group of patients first.
What are the options for a missing tooth today?
Today a missing tooth is replaced with a dental implant, a bridge or a removable denture, and each has trade-offs. Our post on how dental implants work explains the parts and healing process, and our dental implants page describes how we approach implant care. If you are missing a tooth in Jacksonville, contact our office to talk through your options.
Sources
Murashima-Suginami A, Kiso H, Tokita Y, et al. Anti-USAG-1 therapy for tooth regeneration through enhanced BMP signaling. Sci Adv. 2021;7(7):eabf1798. doi:10.1126/sciadv.abf1798. Retrieved via PubMed.
Takahashi K, Kiso H, Mihara E, et al. Development of a new antibody drug to treat congenital tooth agenesis. J Oral Biosci. 2024;66(4):1-9. doi:10.1016/j.job.2024.10.002. Retrieved via PubMed.
Japan Registry of Clinical Trials. Phase I single-administration study of TRG035 in healthy adults (jRCT2051240154). Retrieved October 6, 2026.
About the author. CJ Henley, DMD, is a general dentist in Jacksonville whose practice focuses on cosmetic and restorative dentistry, dental implants and dental care around head and neck cancer. Meet Dr. Henley.
CJ Henley, DMD, PA · 3675 Hendricks Avenue, Jacksonville, FL 32207 · 904-398-1549
Updated October 2026.