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DuPont: Moving probiotics beyond the gut to improve oral health

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The frontiers of microbiome research and probiotic development are expanding quickly. Having begun with digestive and immune health, researchers are now validating links between microorganisms and human wellbeing in every part of the body from the scalp to the feet.1,2​ DuPont is driving the expansion, leading to the introduction of an oral health probiotic and planned launches of cognitive health products.

In recent years, researchers have analyzed how the microbiota in environments such as the nasal airways affect human health, while gathering data on the body-wide effects of microorganisms found in the gut.3–5​ Following this research, the idea that the effect of the microbiome is limited to digestive health, or even digestive and immune health, is obsolete.

The oral microbiome is a particularly strong example of the importance of microorganisms outside of the gut. Research shows more than 700 species of bacteria live in the mouth, making it the second most diverse microbial community in the body.6​ The large number of different bacteria found in the mouth reflects its diverse habitats, which range from the hard surfaces of the teeth to the soft tissue of the cheeks.

Complex colonies of different bacteria attach to surfaces as biofilms. These bacterial biofilms, which underpin dental plaque, influence human health.7​ The diseases associated with problems in the oral microbiome extend throughout the body. Cardiovascular disease, pneumonia, rheumatoid arthritis and pancreatic cancer are just some of the conditions linked to the oral microbiome.8

The oral microbiome is also implicated in in caries, gingivitis, periodontitis and other conditions local to the mouth. In the late 1800s, researchers thought overgrowth of dental plaque was the cause of such oral health problems.9​ However, the development of better techniques for analyzing bacterial communities revealed a more nuanced picture, suggesting that oral disease is driven by shifts in the types of microorganisms found in biofilms, not the volume of the biofilms themselves.10

That knowledge has major implications. Around 80% of people aged 35 years and older suffer from periodontitis or other gum complaints.11​ Periodontitis, a gum infection characterized by the presence of deep spaces around the teeth, is linked with oral heath problems such as tooth loss and systemic issues. Additionally, treating periodontitis in Type II diabetics, heart disease and stroke patients is associated with double-digit reductions in medical costs and hospital admissions.

Validating an oral health probiotic

The evidence linking dysbiosis in the mouth to local and systemic health problems suggests a role for probiotics in the management of oral health. DuPont, as part of its push to expand the probiotic field beyond digestive and immune health, has investigated the role of microbiome in oral health and developed a clinically tested targeted product. 

DuPont’s oral health product, branded HOWARU® Smile, contains Bifidobacterium lactis​ HN019. Studies in rats linked HN019 alongside standard care for periodontitis, a dental procedure known as scaling and root planing, to positive outcomes including reduced dental bone loss.12,13

Encouraged by the findings, a clinical trial of HN019 in 41 chronic periodontitis patients was conducted.14​ The study randomized participants to receive oral HN019 lozenges or placebo for 30 days and tracked them over the 90 days after they underwent scaling and root planing. Subjects who took HN019 had a statistically significant decrease in probing pocket depth and gain in clinical attachment loss.

At baseline, the subjects had deep dental pockets measured more than 7mm, indicating that they had severe periodontitis. After 90 days, the pockets of subjects who received HN019 had shrunk by 3.5mm, putting them on the threshold of gingivitis — a nondestructive form of gum disease — and moderate periodontitis. In contrast, the pockets of the control group only shrank by 2mm, meaning those participants ended the trial on the border between moderate and severe periodontitis.

Other endpoints also suggested HN019 may have positive effects on oral health. Subjects who took HN019 experienced less bleeding on probing and reduced levels of proinflammatory biomarkers.

An analysis of microbial complexes of gingival plaque from the treatment and control groups offers a potential explanation for the positive outcomes. Over the 90-day trial, levels of Porphyromonas gingivalis​ and Treponema denticola​, bacterial strains associated with periodontitis, fell by more in the HN019 group than in the control group. Conversely, levels of Actinomyces naeslundii ​and Streptococcus mitis ​rose in the HN019 group but were flat in the control group. The differences were statistically significant.

Meeting demand for novel probiotics

The clinical data create an opportunity for the probiotic industry. HOWARU® Smile promotes a shift to a healthy oral microbiota, improves clinical parameters and complements usual care, scaling and root planning, helping to support gum health, oral health and overall healthy mouth providing customers with evidence to support the expansion of probiotics into oral health.

There is evidence that such messages resonate with consumers. A 2019 survey found 75% of people in the UK think poor oral health can have a significant impact on general health and 84% of people think taking good care of teeth and gums cuts the risk of needing expensive, invasive procedures later.15

These concerns drive consumer spending. US census data and Simmons National Consumer Survey results suggest 2m Americans spend more than $250 on oral care products every three months.16​ DuPont now has the clinical data to support the addition of probiotics based on its HOWARU Smile to these consumers’ oral care routines.

DuPont’s work to bring the benefits of probiotics to the oral care space is part of a wider effort at the company to expand the field beyond digestive and immune health. That effort has led researchers at DuPont to explore and advance understanding of links between different parts of the microbiome and a wide range of health variables.

HOWARU Smile is the first of an anticipated series of products derived from this research. In 2020, DuPont will introduce HOWARU® Calm, moving the probiotic industry into the management of stress, and continue exploring the effect of modulating the microbiome on cognitive health and other aspects of human wellbeing.

Through this work, DuPont and its partners stand to expand the frontiers of the probiotic industry, building on growing knowledge of the role of the microbiome to deliver products that put consumers in control of more and more aspects of their health.

 

References

1.      Polak-Witka, K., Rudnicka, L., Blume-Peytavi, U. & Vogt, A. The role of the microbiome in scalp hair follicle biology and disease. Exp. Dermatol.​ (2019). doi:10.1111/exd.13935

2.      Jneid, J., Lavigne, J. P., La Scola, B. & Cassir, N. The diabetic foot microbiota: A review. Human Microbiome Journal5-6​, 1–6 (2017).

3.      Mahdavinia, M., Keshavarzian, A., Tobin, M. C., Landay, A. L. & Schleimer, R. P. A comprehensive review of the nasal microbiome in chronic rhinosinusitis (CRS). Clin. Exp. Allergy46​, 21–41 (2016).

4.      Bjerre, R. D., Bandier, J., Skov, L., Engstrand, L. & Johansen, J. D. The role of the skin microbiome in atopic dermatitis: a systematic review. Br. J. Dermatol.177​, 1272–1278 (2017).

5.      Nguyen, T. T., Kosciolek, T., Eyler, L. T., Knight, R. & Jeste, D. V. Overview and systematic review of studies of microbiome in schizophrenia and bipolar disorder. J. Psychiatr. Res.99​, 50–61 (2018).

6.      Kilian, M. et al.​ The oral microbiome - an update for oral healthcare professionals. Br. Dent. J.221​, 657–666 (2016).

7.      Zarco, M. F., Vess, T. J. & Ginsburg, G. S. The oral microbiome in health and disease and the potential impact on personalized dental medicine. Oral Dis.18​, 109–120 (2012).

8.      Jia, G. et al.​ The oral microbiota - a mechanistic role for systemic diseases. Br. Dent. J.224​, 447–455 (2018).

9.      Rosier, B. T., De Jager, M., Zaura, E. & Krom, B. P. Historical and contemporary hypotheses on the development of oral diseases: are we there yet? Front. Cell. Infect. Microbiol.4​, 92 (2014).

10.    Nath, S. G. & Raveendran, R. Microbial dysbiosis in periodontitis. J. Indian Soc. Periodontol.17​, 543–545 (2013).

11.    DOSSIER ON PERIODONTAL DISEASE. EFP​ Available at: https://www.efp.org/publications/EFP_Dossier_on_Periodontal_Disease_2018.pdf. (Accessed: 18th November 2019)

12.    Oliveira, L. F. F. et al.​ Benefits of Bifidobacterium animalis subsp. lactis Probiotic in Experimental Periodontitis. J. Periodontol.88​, 197–208 (2017).

13.    Ricoldi, M. S. T. et al.​ Effects of the probiotic Bifidobacterium animalis subsp. lactis on the non-surgical treatment of periodontitis. A histomorphometric, microtomographic and immunohistochemical study in rats. PLoS One12​, e0179946 (2017).

14.    Invernici, M. M. et al.​ Effects of Bifidobacterium probiotic on the treatment of chronic periodontitis: A randomized clinical trial. J. Clin. Periodontol.45​, 1198–1210 (2018).

15.    Consumer Oral Health Survey 2019. SimplyHealth​ Available at: https://www.simplyhealth.co.uk/content/dam/simplyhealth/denplan/documents/simplyhealth-COHS-2019.pdf. (Accessed: 18th November 2019)

16.    U.S.: total amount spent on oral care products 2019 | Statista. Statista​ Available at: https://www.statista.com/statistics/317866/us-households-total-amount-spent-on-oral-care-products-past-3-months/. (Accessed: 18th November 2019)

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