Human microbiome therapeutics is a hugely exciting new field of research with almost limitless potential. So far the growing industry's focus has largely been on the gut, but there are numerous opportunities in other areas too. In new series we go Beyond the Gut, exploring the therapeutic potential of the oral and skin microbiome, gut/brain axis, gut/liver axis and around cardiovascular diseases. Here we look at the oral microbiome. Download the full Microbiome Therapeutics: Beyond the Gut series as a whitepaper here.
The mouth is home to a diverse microbial community, with over 700 species of bacteria colonizing both the teeth and soft tissues. Changes to this microbiome can have a distinct impact on oral health, allowing the growth of conditions such as caries, gingivitis and periodontitis. As such, advances in this space are crucial to the improvement of oral healthcare.
Where are we now?
According to Grandview Research, the global oral care market size was valued at USD 28.0 billion in 2017, with a projected growth rate of 5.0% up to 2025. Toothbrushes and toothpaste accounted for about 50% of the market, followed by mouthwash products (20%), dental products and dental accessories (15% each). The geriatric segment has been growing fastest, and innovation in the sector has increased consumer interest and purchases of new products.
As the relationship between the oral microbiome and the host is dynamic, biological changes in a person's life can affect the microbiota. Some of these changes include physiological changes (such as age or hormonal changes in puberty and pregnancy) to which adaptation is necessary to bypass detrimental effects in oral health. Poor oral hygiene, gingival inflammation and some lifestyle choices such as dietary habits and smoking can contribute to poor oral microbiome health.
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The new understanding of the oral microbiome is shaping how we think about dental caries, periodontal and systemic diseases. While the traditional view held that these diseases were caused by a small number of pathogens, we now consider the oral microbiome to be a finely tuned ecosystem, a balanced (or unbalanced) community of microorganisms that mediates not only oral health and disease but also some systemic diseases.
Research areas and companies
Many interesting companies are operating in this space such as Oragenics, Seres Therapeutics, DoseBiome, Rebiotix and C3J Therapeutics.
Oragenics is focused on developing effective treatments for oral mucositis as well as other diseases and conditions of the oral cavity, throat, and esophagus. As such, their objective is to develop safe genetically engineered bacterial strains designed to produce, deliver and release therapeutics locally at oral disease sites to prevent or cure diseases. Their lead compound in oral mucositis, AG 013, has just completed phase IB, and the company is now undertaking further studies before proceeding with a phase 2 clinical trial.
Seres Therapeutics has been targeting the oral biome to treat Clostridium difficile infection (CDI). The SER-262 candidate is an investigational oral microbiome therapeutic for patients with primary CDI which is currently in a Phase 1b study. Meanwhile, another compound, SER-109, is an investigational oral microbiome therapeutic for the prevention of recurrent Clostridium difficile infection in adults with multiply recurrent CDI. This product is currently in phase 3.
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DoseBiome is focused on innovative oral microbiome research that improves the microbial ecosystem in the mouth by preventing diseases such as dental caries and periodontal conditions. The objective is the development of pre/probiotic consumer products that selectively reduce bad bacteria while promoting healthy populations of the good.
Finally, C3J Therapeutics is a mid-sized US-based clinical-stage biotechnology company focused on the discovery and development of novel targeted antimicrobials. One of its lead compounds, C16G2, targets dysbiosis of the oral microbiome, and has completed phase 2 clinical trials. As for Rebiotix, they have in their pipeline a compound (RBX7455) that is an oral Microbiota Restoration Therapy™ drug platform targeted at Clostridium difficile infection prevention.
Potential growth and discovery
Ongoing research in how the oral microbiome interacts with other body microbiomes is critical to understanding our body and potential interaction. For example, research has linked bacteria in the oral microbiome and both esophageal and gastric cancer, suggesting that changing bacteria in the mouth may represent an innovative methodology to prevent these cancers.
Emerging research is focusing on the study of the oral microbiome for predicting diseases as it has been linked not only with oral health but also as an indicator for screening and monitoring Crohn’s disease and ulcerative colitis patients. In parallel with the study of the gut microbiome, emerging research is focusing on how the oral microbiome develops during early childhood and to what extent external factors influence its colonization and development.
Some of the bacteria currently under study includes Tannerella forsythia which is linked to an increased risk of esophageal adenocarcinoma (EAC), whereas Porphyromonas gingivalis has been associated with a higher risk of esophageal squamous cell carcinoma (ESCC). Other studies have found that the increase in certain oral pathogens while reducing bacterial diversity led to an increased risk of precancerous lesions of gastric cancer (PLGC). Also, chronic periodontal inflammation is associated with a variety of cancers, suggesting that there is a pathogen associated with this inflammation and could be an important contributing factor.
Some researchers believe that saliva samples provide a good representation not only of overall oral health but also of systemic health, and there are many research teams around the world working on that specific aspect. In general, saliva is considered a body probe where signals of our health are constantly secreted. For instance, diabetes and several types of cancer can be detected in saliva if you look at the right molecules. Further studies are needed to understand the association between oral and gut microbiota and the potential impact on infant health. For example, oral bacteria are needed for our systemic health, but they must stay in the mouth: in patients with a compromised immune system, oral bacteria can invade the gut or the lungs and contribute to inflammation and disease.
Funding, investments and partnerships
DoseBiome, was accepted as one of 50 resident companies working at JLABS @ Toronto, which is a Johnson & Johnson Innovation incubator aimed at helping nurture healthcare start-ups. Also, in July 2018, Oragenics announced the closing of an underwritten public offering of units for gross proceeds of approximately USD 13.8 million. In January 2019, C3J Therapeutics merged with AmpliPhi Biosciences, a company focused on the development of precisely targeted bacteriophage therapeutics for antibiotic-resistant infections. Certain existing C3J shareholders have committed to invest $10 million in the combined company.
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