Much of the interest in xylitol stems from its use in dentistry for prophylaxis against decay. The administration of xylitol in chewing gum and oral pastilles to schoolchildren in Finland has been the mainstay of a successful public health program for stemming that country’s epidemic of pediatric dental caries. Early intervention via swabbing the teeth and gums in infancy has likewise proved effective in protecting teeth.13

Xylitol appears to exert specific activity against Streptococcus mutans biofilms, implicated in dental caries and periodontal disease.14 It is thought that xylitol exerts its anti-cariogenic effects by causing S mutans organisms to auto-destruct via a “Trojan horse” mechanism: the uptake of xylitol through the microbial fructose phosphotransferase system and formation of a toxic metabolite, xylitol-5-phosphate, in the cells. Subsequent accumulation of xylitol-5-phosphate interferes with carbohydrate metabolism and inhibits bacterial growth.

Other species of cariogenic bacteria are said to be susceptible to the biofilm-preventing actions of xylitol; moreover, the application of xylitol reduces acid production by oral pathogens, a key mechanism of dental enamel erosion and periodontal tissue invasion.15


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The apparent success of xylitol in attenuating dental biofilms has led to an exploration of its potential application in chronic, refractory infections of the respiratory tract and in persistent wounds. In a recent study of 20 volunteers, a 10-day course of xylitol irrigation resulted in a greater reduction of the symptoms of chronic rhinosinusitis than did saline irrigation.16 Finnish researchers demonstrated an antiadherence effect of 5% xylitol on pathogens implicated in otitis media.17 They theorized that nasal inhalation of a xylitol solution might confer protection against bacterial colonization of the middle ear given the anatomical communication of the nasal passages with the eustachian tubes.

The topical application of xylitol in combination with lactoferrin has been explored as a means of facilitating wound healing. Researchers recently demonstrated the superiority of a wound dressing containing lactoferrin/xylitol hydrogel in combination with silver over a commercially available hydrogel wound dressing in reducing wound biofilms.18

An interesting corollary to the wound-healing capabilities of xylitol has been proposed in atopic dermatitis or eczema. Because a common feature of chronic refractory dermatitis is colonization with epidermal Staphylococcus aureus, it has been theorized that biofilm formation may play a role in the persistence of this skin condition; difficulty in eradicating dermatitis or eczema, even with repeated antibiotic administration, may be due to the persistence of S aureus biofilms. Researchers who applied emollient creams containing xylitol combined with farnesol (an acrylic sesquiterpene alcohol derived from the oil of plants, such as citronella oil) achieved the eradication of superficial staph biofilms after just 7 days.19


Some researchers have proposed that acne is a biofilm disorder, and future strategies against acne may involve the use not only of topical and systemic antibiotics but also surface agents in the hope of creating an unfavorable environment for the acne biofilm.20

Cautions regarding xylitol

Xylitol is safe for humans. It has been approved internationally for use in oral care products and pharmaceuticals and as a sugar substitute for decades. Xylitol, like most sugar alcohols, may have a laxative effect when taken in large amounts. This is because, until the digestive system adapts, xylitol may not be fully digested and has an osmotic effect on the gastrointestinal tract.

The safety profile of xylitol for nonprimate species differs from that for humans in that xylitol can trigger the release of insulin from the pancreas. Because xylitol is a nonnutritive sweetener, it has a minimal caloric effect. If a dog ingests xylitol, profound hypoglycemia and even liver failure can result.

The Pet Poison Helpline has reported more than 1500 calls for xylitol poisoning over the last 5 years. Symptoms of xylitol ingestion in animals may include the following:

• Vomiting

• Weakness

• Incoordination or difficulty walking

• Lethargy

• Tremors

• Seizures

• Coma

It is therefore imperative to store sweet-tasting products that contain xylitol securely out of the reach of inquisitive pets. Human toothpastes containing xylitol should not be used for pets. If accidental ingestion by a pet is suspected, prompt referral to a veterinarian for supportive care is mandatory.21

Current strategies

Ultimately, the challenge of biofilm infections is likely to be addressed in the future via the deployment of high-tech pharmaceutical breakthroughs, perhaps alongside innovative strategies borrowed from nature. Meanwhile, as we await definitive solutions, the prevention and treatment of biofilm disorders must remain improvisational, perhaps involving the deft application of antimicrobials together with novel inhibitory or antiadherence substances. Because of the urgency of reducing the toll of serious infections now proving difficult to eradicate with antibiotics alone, intense research efforts will continue to focus on unraveling the mysteries of this elusive foe.

Ronald Hoffman, MD, CNS, is the founder and medical director of the Hoffman Center in New York City.

References

  1. Paredes J, Onso-Arce M, Schmidt C, et al. Smart central venous port for early detection of bacterial biofilm-related infections. Biomed Microdevices. 2014;16:365-374.

  2. Monroe D. Looking for chinks in the armor of bacterial biofilms. PLoS Biol. 2007;5:e307.

  3. Høiby N, Bjarnsholt T, Moser C, et al. ESCMID guideline for the diagnosis and treatment of biofilm infections. Clin Microbiol Infect. 2015;21(Suppl 1):S1-S25.

  4. Wu H, Moser C, Wang H-Z, Høiby N, Song Z-J. Strategies for combating bacterial biofilm infections. Int J Oral Sci. 2015;7:1-7.

  5. Song Z, Kong KF, Wu H, et al. Panax ginseng has anti-infective activity against opportunistic pathogen Pseudomonas aeruginosa by inhibiting quorum sensing. Phytomedicine. 2010;17:1040-1046.

  6. Bjarnsholt T, Jensen PØ, Rasmussen TB, et al. Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections. Microbiology. 2005;151(Pt 12):3873-3880.

  7. Wu H, Lee B, Yang L, et al. Effects of ginseng on Pseudomonas aeruginosa motility and biofilm formation. FEMS Immunol Med Microbiol. 2011;62:49-56.

  8. Romero D, Sanabria-Valentin E, Vlamakis H, Kolter R. Biofilm inhibitors that target amyloid proteins. Chem Biol. 2013;20:102-110.

  9. Singh PK, Parsek MR, Greenberg EP, Welsh MJ. A component of innate immunity prevents bacterial biofilm development. Nature. 2002;417:552-555.

  10. Banin E, Brady KM, Greenberg EP. Chelator-induced dispersal and killing of Pseudomonas aeruginosa cells in a biofilm. Appl Environ Microbiol. 2006;72:2064-2069.

  11. Lequette Y, Boels G, Clarisse M, Faille C. Using enzymes to remove biofilms of bacterial isolates sampled in the food industry. Biofouling. 2010;26:421-431.

  12. Söderling EM, Hietala-Lenkkeri AM. Xylitol and erythritol decrease adherence of polysaccharide-producing oral streptococci. Curr Microbiol. 2010;60:25-29.

  13. Mäkinen KK, Järvinen KL, Anttila CH, Luntamo LM, Vahlberg T. Topical xylitol administration by parents for the promotion of oral health in infants: a caries prevention experiment at a Finnish Public Health Centre. Int Dent J. 2013;63:210-224.

  14. Arunakul M, Thaweboon B, Thaweboon S, Asvanund Y, Charoenchaikorn K. Efficacy of xylitol and fluoride mouthrinses on salivary mutans streptococci. Asian Pac J Trop Biomed. 2011;1:488-490.

  15. Badet C, Furiga A, Thébaud N. Effect of xylitol on an in vitro model of oral biofilm. Oral Health Prev Dent. 2008;6:337-341.

  16. Weissman JD, Fernandez F, Hwang PH. Xylitol nasal irrigation in the management of chronic rhinosinusitis: a pilot study. Laryngoscope. 2011;121:2468-2472.

  17. Kontiokari T, Uhari M, Koskela MJ. Antiadhesive effects of xylitol on otopathogenic bacteria. J Antimicrob Chemother. 1998;41:563-565.

  18. Ammons MC, Ward LS, James GA. Anti-biofilm efficacy of a lactoferrin/xylitol wound hydrogel used in combination with silver wound dressings. Int Wound J. 2011;8:268-273.

  19. Nusbaum A, Kirsner R, Charles CA. Biofilms in dermatology. Skin Therapy Lett. 2012;17:1-5.

  20. Burkhart CN, Burkhart CG. Microbiology’s principle of biofilms as a major factor in the pathogenesis of acne vulgaris. Int J Dermatol. 2003;42:925-927.

  21. Xylitol toxicity in dogs. VCA Animal Hospitals website. http://www.vcahospitals.com/main/pet-health-information/article/animal-health/xylitol-toxicity-in-dogs/4340.