An innovative approach to oral dysbiosis in dogs 

Oral dysbiosis is a driver of dental disease in dogs. Here’s how a unique new approach targets the oral microbiome to block pathogen growth and restore balance.

Oral dysbiosis, an imbalance of the microbial community that inhabits the oral cavity, strongly correlates with dental disease in humans, dogs, and other animals. Oral dysbiosis occurs concomitant with signs of gingivitis and periodontal disease in healthy animals after challenges with Porphyromonas gingivalis.1

Diagnosis

A hallmark of oral dysbiosis is the loss of microbial diversity within the oral cavity. In lower GI and skin microbiome research, loss of diversity strongly correlates with an increase in inflammation.2,3 Recent work  has characterized the in situ inflammatory responses driven by a dysbiotic microbiome. Briefly, it has been shown to elicit characteristic Th17 immune responses, including increases in IL-6 and IL-23 cytokine levels and an accumulation of neutrophils surrounding the affected tissue.7

A second hallmark of oral dysbiosis is the increased presence (burden) of pathogenic microbes, such as Porphyromonas sp., Tannerella sp., Treponema sp., and/or abnormally high levels of commensal microbes such as Actinomyces sp. or Fusobacterium sp.4-6

A third hallmark of oral dysbiosis is the decrease in microbes such as Lactic Acid bacteria known to be protective (they either regulate healthy immune balance or promote healthy barrier functions).

Pinpointing the cause

Drivers of oral dysbiosis are diet, age, exercise, exposure to antibiotics, some medications and an alteration of the dog’s health (particularly having to do with salivary output and liver function).

Figure 1. Change in oral pathogen burden in five days. Briefly, dogs were given Protektin42 in drinking water each day for five days. Oral samples were collected by swab and cultured on media. Baseline levels of dental and enteric pathogens were collected from a canine participant.   (Left petri  plate, baseline) Aspergillus predominated growth on TSA blood agar (upper half plate) and a mixture of E. coli, Salmonella, and Klebsiella predominated on the bile salts agar (lower half plate).   (Right petri plate, day five) non-hemolytic polymicrobial population predominated the TSA blood agar (upper half plate); no enteric growth was observed in the lower half of the plate.  Similar results observed in anaerobic culture studies with Porphyromonas sp, Tanerella sp and T. denticola burdens at baseline vs day five. Data not shown.

A targeted treatment approach

We developed an approach to rehabilitate a dysbiotic oral microbiome in canines. Briefly, an ideal approach would be safe and well-tolerated for daily consumption, work directly on the oral microbiome upon contact, and induce changes in the composition of the oral microbiome in a relatively short period of time.

After screening hundreds of GRAS (generally recognized as safe) ingredients with ideal safety profiles for daily consumption in canines, we identified several target ingredients that selectively (i) blocked the growth of pathogenic bacteria and fungus in the oral cavity, (ii) but induced the growth of beneficial microbes in co-culture and in oral  biofilm studies.

Figure 2. Rehabilitation of oral dysbiosis and improved oral health. Case study involving a 10 year old Sheltie with moderate gingivitis. Baseline image of gingiva showing redness and mild swelling. Day 60 image of gingiva showing significantly less redness and reduced swelling after daily administration of Protektin42.

Formulation studies showed a synergism when used in combination that were ideal for use in canine, particularly when administered in drinking water. This synergistic combination of ingredients is called Protektin42™ and has been shown in over 95 dogs to block pathogen growth in as little as five days, and to facilitate the growth of beneficial oral microbes in that same timeframe. The result of which can be seen in 16s rDNA sequencing (data not shown) and culture-based results (Figure 1) and with continued use, can promote oral health (Figure 2). Protektin42 is sold under the brand name Teef for Life, which can be found at teefhealth.com.

References
1
https://www.frontiersin.org/articles/10.3389/fcimb.2020.00092/full

2https://academic.oup.com/ibdjournal/article/13/6/675/4644945

3https://link.springer.com/article/10.1007/s40257-020-00531-1

4https://iai.asm.org/content/68/6/3140

5https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129341/

6https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366302/

7https://stm.sciencemag.org/content/10/463/eaat0797?intcmp=trendmd-stm

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Emily Stein, PhD
Emily Stein, Ph.D. founded Primal Health (TEEF for Life) in 2017 to focus on improving the dental health of both humans and animals by producing oral microbiome modulation products. She has spent 12 years developing Selective Microbial Metabolism Regulation Technology (SMMRT™) at Primal Therapies, Inc., which is focused on using metabolic influencers to re-engineer disease-causing bacterial biofilms into those that are health-promoting, to decrease inflammation and to improve outcomes. Prior to that, she spent 7 years as a research fellow at Stanford University in Rheumatology and Immunology focused on the neuro-endocrine-immune axis in autoimmune and chronic inflammatory diseases. She holds a Ph.D. in Microbiology from the University of California at Berkeley where she studied inter- and intra-cellular signaling pathways involved in stress response and community development in bacteria and received her B.S. in Microbiology and Immunology at the University of Iowa where she studied the interaction between M. tuberculosis and innate immune cells.

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