POSTBIOTICS

One Step Ahead of Probiotics

SOME DEFINITIONS IN
THE “BIOTIC” WORLD

The term “biotic” originates from the Greek word biōtikós meaning “pertaining to life,” and refers to the “biological ecosystem made up of living organisms together with their physical environment.”1Wegh C.A.M. et al., 2019

Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.”2Hill C. et al., 2014

A prebiotic is a “substrate that is selectively utilized by host microorganisms conferring a health benefit.”3Gibson et al., 2017

Synbiotics are “synergistic mixtures of probiotics and prebiotics that beneficially affect the host by improving the survival and colonization of live beneficial microorganisms in the gastrointestinal tract of the host.4FAO/WHO, 20015FAO/WHO, 2002

A postbiotic is a “bioactive compound produced during a fermentation process that supports health and/or wellbeing,6Collado et al., 2019in a direct or indirect way.”7Tsilingiri et al., 2013 An important point of this definition is that the microorganism underlying the effect does not need to be alive. Therefore, non-viable, inactivated or heat-killed microbial cells (also called parabiotics), microbial metabolites (proteins, lipids, carbohydrates, vitamins, organic acids), cell wall components and other complex molecules from the extracellular matrix of the bacteria can be considered as postbiotics.8.12George Kerry et al., 2018 Malagón-Rojas et al., 2020 Taverniti et al., 2011 Aguilar-Toalá et al., 2018  Konstantinov et al., 2013

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1. Wegh CAM, Geerlings SY, Knol J, Roeselers G, Belzer C. Postbiotics and Their Potential Applications in Early Life Nutrition and Beyond. Int J Mol Sci. 2019 Sep 20;20(19). pii: E4673. doi: 10.3390/ijms20194673. Review. PubMed PMID:31547172; PubMed Central PMCID: PMC6801921.

2. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014 Aug;11(8):506-14. doi: 10.1038/nrgastro.2014.66. Epub 2014 Jun 10. PubMed PMID: 24912386.

3. Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, Scott K, Stanton C, Swanson KS, Cani PD, Verbeke K, Reid G. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP)consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017 Aug;14(8):491-502. doi: 10.1038/nrgastro.2017.75. Epub 2017 Jun 14. Review. PubMed PMID: 28611480.

4. FAO/WHO. Food and Agriculture Organization of the United Nations/World Health Organization Health and Nutritional Properties of Probiotics in Food including Powder Milk with Live Lactic Acid Bacteria.

5. Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO). Guidelines for the Evaluation of Probiotics in Food. In Joint Fao/Who Working Group on Drafting Guidelines for the Evaluation of Probiotics in Food; WHO: London, ON, Canada, 2002.

6. Collado MC, Vinderola G, Salminen S. Postbiotics: facts and open questions. A position paper on the need for a consensus definition. Benef Microbes. 2019 Oct 14;10(7):711-719. doi: 10.3920/BM2019.0015. Epub 2019 Aug 7. PubMed PMID: 31965850.

7. Tsilingiri K, Rescigno M. Postbiotics: what else? Benef Microbes. 2013 Mar 1;4(1):101-7. doi: 10.3920/BM2012.0046. Review. PubMed PMID: 23271068.

8. George Kerry R, Patra JK, Gouda S, Park Y, Shin HS, Das G. Benefaction of probiotics for human health: A review. J Food Drug Anal. 2018 Jul;26(3):927-939. doi: 10.1016/j.jfda.2018.01.002. Epub 2018 Feb 2. Review. PubMed PMID: 29976412.

9. Malagón-Rojas JN, Mantziari A, Salminen S, Szajewska H. Postbiotics for Preventing and Treating Common Infectious Diseases in Children: A Systematic Review. Nutrients. 2020 Jan 31;12(2). pii: E389. doi: 10.3390/nu12020389. Review. PubMed PMID: 32024037; PubMed Central PMCID: PMC7071176.

10. Taverniti V, Guglielmetti S. The immunomodulatory properties of probiotic microorganisms beyond their viability (ghost probiotics: proposal of paraprobiotic concept). Genes Nutr. 2011 Aug;6(3):261-74. doi:10.1007/s12263-011-0218-x. Epub 2011 Apr 16. PubMed PMID: 21499799; PubMed Central PMCID: PMC3145061.

11. Aguilar-Toalá, J.; Garcia-Varela, R.; Garcia, H.; Mata-Haro, V.; González-Córdova, A.; Vallejo-Cordoba, B.; Hernández-Mendoza, A. Postbiotics: An evolving term within the functional foods field. Trends Food Sci. Technol. 2018, 75, 105–114.

12. Konstantinov SR, Kuipers EJ, Peppelenbosch MP. Functional genomic analyses of the gut microbiota for CRC screening. Nat Rev Gastroenterol Hepatol. 2013Dec;10(12):741-5. doi: 10.1038/nrgastro.2013.178. Epub 2013 Sep 17. PubMed PMID: 24042452.

Probiotics are good for you except when they are not: The opportunity for postbiotics.

The majority of probiotics are lactic acid bacteria (LAB) such as Lactobacillus or Bifidobacterium species. They are Generally Recognized As Safe (GRAS) by the FDA,13O’Toole et al., 2017 and are used for a variety of applications ranging from food industry to clinical practice.2Hill et al., 201413O’Toole et al., 201714Wilkins et al., 2017 However, concern is growing in the scientific and medical communities regarding the safety of probiotic use in vulnerable populations, particularly in younger children and in adults with underlying conditions.15.17Goldstein et al., 2015 Doron et al., 2015 Ohishi et al., 2010

One of the main concerns is that probiotics can move from the area of application to other areas of the body, where they may cause infection.18.25Barraud et al., 2013 Barraud et al., 2010 Honeycut et al., 2007 Suez et al., 2018 Zmora et al., 2018 Kunz et al., 2004 Salminen et al., 2003 Thomas et al., 2010 Another concern is that antibiotic resistance genes present in the probiotic bacteria could be transferred to pathogenic bacteria present in the intestines,26Wong et al., 201527Aceti et al., 2018 since bacterial cells have been known to transfer genes to their neighbors. In addition, specific probiotic strains can express virulence factors, or chemicals that can harm the cells lining the digestive tract28Rowan et al., 2001 or the beneficial bacteria that live there.

Most prebiotics are carbohydrates,29Sanders et al., 2019 long chains of sugar molecules connected end-to-end. Some prebiotics are short chain carbohydrates called oligosaccharides. Prebiotics are believed to regulate the microbiota by promoting the growth of certain species in order to confer a health benefit.3Gibson et al., 2017 However, studies of the microbiome have revealed that the effects of probiotics are not that simple.30Hutkins et al., 2016 Probiotics can stimulate the growth of unexpected or unidentified species of the microbiota.31.33Trompette et al., 2014 Holscher et al., 2015 Salonen et al., 2014

 

Postbiotics would seem to solve most of these issues and limitations. In particular, they are safer than probiotics since the beneficial compounds can be administered without the risk of undesirable bacterial growth.34de Almada et al., 2016

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2. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014 Aug;11(8):506-14. doi: 10.1038/nrgastro.2014.66. Epub 2014 Jun 10. PubMed PMID: 24912386.

3. Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, Scott K, Stanton C, Swanson KS, Cani PD, Verbeke K, Reid G. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP)consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017 Aug;14(8):491-502. doi: 10.1038/nrgastro.2017.75. Epub 2017 Jun 14. Review. PubMed PMID: 28611480.

13. O’Toole PW, Marchesi JR, Hill C. Next-generation probiotics: the spectrum from probiotics to live biotherapeutics. Nat Microbiol. 2017 Apr 25;2:17057. doi:10.1038/nmicrobiol.2017.57. PubMed PMID: 28440276.

14. Wilkins T, Sequoia J. Probiotics for Gastrointestinal Conditions: A Summary of the Evidence. Am Fam Physician. 2017 Aug 1;96(3):170-178. Review. PubMed PMID:28762696.

15. Goldstein EJ, Tyrrell KL, Citron DM. Lactobacillus species: taxonomiccomplexity and controversial susceptibilities. Clin Infect Dis. 2015 May 15;60 Suppl 2:S98-107. doi: 10.1093/cid/civ072. Review. PubMed PMID: 25922408.

16. Doron S, Snydman DR. Risk and safety of probiotics. Clin Infect Dis. 2015 May 15;60 Suppl 2:S129-34. doi: 10.1093/cid/civ085. Review. PubMed PMID: 25922398; PubMed Central PMCID: PMC4490230.

17. Ohishi A, Takahashi S, Ito Y, Ohishi Y, Tsukamoto K, Nanba Y, Ito N, Kakiuchi S, Saitoh A, Morotomi M, Nakamura T. Bifidobacterium septicemia associated withpostoperative probiotic therapy in a neonate with omphalocele. J Pediatr. 2010 Apr;156(4):679-81. doi: 10.1016/j.jpeds.2009.11.041. PubMed PMID: 20303445.

18. Barraud D, Bollaert PE, Gibot S. Impact of the administration of probiotics on mortality in critically ill adult patients: a meta-analysis of randomized controlled trials. Chest. 2013 Mar;143(3):646-655. doi: 10.1378/chest.12-1745.Review. PubMed PMID: 23460153.

19. Barraud D, Blard C, Hein F, Marçon O, Cravoisy A, Nace L, Alla F, Bollaert PE, Gibot S. Probiotics in the critically ill patient: a double blind, randomized,placebo-controlled trial. Intensive Care Med. 2010 Sep;36(9):1540-7. doi: 10.1007/s00134-010-1927-0. Epub 2010 May 26. PubMed PMID: 20502866.

20.Honeycutt TC, El Khashab M, Wardrop RM 3rd, McNeal-Trice K, Honeycutt AL,Christy CG, Mistry K, Harris BD, Meliones JN, Kocis KC. Probiotic administration and the incidence of nosocomial infection in pediatric intensive care: a randomized placebo-controlled trial. Pediatr Crit Care Med. 2007 Sep;8(5):452-8; quiz 464. PubMed PMID: 17693918.

21.Suez J, Zmora N, Zilberman-Schapira G, Mor U, Dori-Bachash M, Bashiardes S,Zur M, Regev-Lehavi D, Ben-Zeev Brik R, Federici S, Horn M, Cohen Y, Moor AE,Zeevi D, Korem T, Kotler E, Harmelin A, Itzkovitz S, Maharshak N, Shibolet O,Pevsner-Fischer M, Shapiro H, Sharon I, Halpern Z, Segal E, Elinav E.Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT. Cell. 2018 Sep 6;174(6):1406-1423.e16. doi:10.1016/j.cell.2018.08.047. PubMed PMID: 30193113.

22.Zmora N, Zilberman-Schapira G, Suez J, Mor U, Dori-Bachash M, Bashiardes S,Kotler E, Zur M, Regev-Lehavi D, Brik RB, Federici S, Cohen Y, Linevsky R,Rothschild D, Moor AE, Ben-Moshe S, Harmelin A, Itzkovitz S, Maharshak N, Shibolet O, Shapiro H, Pevsner-Fischer M, Sharon I, Halpern Z, Segal E, Elinav E.Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features. Cell. 2018 Sep 6;174(6):1388-1405.e21. doi: 10.1016/j.cell.2018.08.041. PubMed PMID: 30193112.

23. Kunz AN, Noel JM, Fairchok MP. Two cases of Lactobacillus bacteremia during probiotic treatment of short gut syndrome. J Pediatr Gastroenterol Nutr. 2004 Apr;38(4):457-8. PubMed PMID: 15085028.

24. Salminen MK, Rautelin H, Tynkkynen S, Poussa T, Saxelin M, Valtonen V, Järvinen A. Lactobacillus bacteremia, clinical significance, and patient outcome, with special focus on probiotic L. rhamnosus GG. Clin Infect Dis. 2004 Jan 1;38(1):62-9. Epub 2003 Dec 4. PubMed PMID: 14679449.

25. Thomas DW, Greer FR; American Academy of Pediatrics Committee on Nutrition; American Academy of Pediatrics Section on Gastroenterology, Hepatology, and Nutrition. Probiotics and prebiotics in pediatrics. Pediatrics. 2010 Dec;126(6):1217-31. doi: 10.1542/peds.2010-2548. Epub 2010 Nov 29. Review. PubMed PMID: 21115585.

26. Wong A, Ngu DY, Dan LA, Ooi A, Lim RL. Detection of antibiotic resistance in probiotics of dietary supplements. Nutr J. 2015 Sep 14;14:95. doi:10.1186/s12937-015-0084-2. PubMed PMID: 26370532; PubMed Central PMCID: PMC4568587.

27. Aceti A, Beghetti I, Maggio L, Martini S, Faldella G, Corvaglia L. Filling the Gaps: Current Research Directions for a Rational Use of Probiotics in Preterm Infants. Nutrients. 2018 Oct 10;10(10). pii: E1472. doi: 10.3390/nu10101472. Review. PubMed PMID: 30308999; PubMed Central PMCID: PMC6213418.

28. Rowan NJ, Deans K, Anderson JG, Gemmell CG, Hunter IS, Chaithong T. Putative virulence factor expression by clinical and food isolates of Bacillus spp. after growth in reconstituted infant milk formulae. Appl Environ Microbiol. 2001 Sep;67(9):3873-81. PubMed PMID: 11525980; PubMed Central PMCID: PMC93104.

29. Sanders ME, Merenstein DJ, Reid G, Gibson GR, Rastall RA. Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nat Rev Gastroenterol Hepatol. 2019 Oct;16(10):605-616. doi:10.1038/s41575-019-0173-3. Epub 2019 Jul 11. Review. PubMed PMID: 31296969.

30. Hutkins RW, Krumbeck JA, Bindels LB, Cani PD, Fahey G Jr, Goh YJ, Hamaker B, Martens EC, Mills DA, Rastal RA, Vaughan E, Sanders ME. Prebiotics: why definitions matter. Curr Opin Biotechnol. 2016 Feb;37:1-7. doi: 10.1016/j.copbio.2015.09.001. Epub 2015 Sep 29. Review. PubMed PMID: 26431716; PubMed Central PMCID: PMC4744122.

31. Trompette A, Gollwitzer ES, Yadava K, Sichelstiel AK, Sprenger N, Ngom-Bru C, Blanchard C, Junt T, Nicod LP, Harris NL, Marsland BJ. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med. 2014 Feb;20(2):159-66. doi: 10.1038/nm.3444. Epub 2014 Jan 5. PubMed PMID: 24390308.

32. Holscher HD, Caporaso JG, Hooda S, Brulc JM, Fahey GC Jr, Swanson KS. Fiber supplementation influences phylogenetic structure and functional capacity of the human intestinal microbiome: follow-up of a randomized controlled trial. Am J Clin Nutr. 2015 Jan;101(1):55-64. doi: 10.3945/ajcn.114.092064. Epub 2014 Nov 12. PubMed PMID: 25527750.

33. Salonen A, Lahti L, Salojärvi J, Holtrop G, Korpela K, Duncan SH, Date P, Farquharson F, Johnstone AM, Lobley GE, Louis P, Flint HJ, de Vos WM. Impact of diet and individual variation on intestinal microbiota composition and fermentation products in obese men. ISME J. 2014 Nov;8(11):2218-30. doi: 10.1038/ismej.2014.63. Epub 2014 Apr 24. PubMed PMID: 24763370; PubMed Central PMCID: PMC4992075.

34. de Almada, C. N., Almada, C. N., Martinez, R. C. R., & Sant ́Ana, A. S. (2016). Paraprobiotics: Evidences on their ability to modify biological responses, inactivation methods and perspectives on their application in foods. Trends in Food Science & Technology, 58, 96–114.

What is the mechanism of action of postbiotics?

Contrary to common belief, the bacterial cells in probiotics do not need to be living in order to have a beneficial effect35Piqué et al., 2019—postbiotics can mimic the action of probiotics through the non-living components of microbial cells and the chemicals they produced when alive. Postbiotics mainly act at two levels:

Effect on the microbial community interactions

Postbiotics can suppress pathogens through the effects of organic acids and bacteriocins (chemicals bacteria release to inhibit the growth of other bacteria). They can also prevent pathogen adhesion, invasion and the formation of bacterial biofilms1Wegh et al., 201935Piqué et al., 2019 because some cell wall components, such as exopolysaccharides (EPS), can reduce the ability of pathogens to adhere to surfaces.35.37Piqué et al., 2019 Sarkar et al., 2016 Castro-Bravo et al., 2018 Surface layer proteins (SLP) can contribute to the co-aggregation (immobilization) of pathogenic bacteria.38Lebeer et al., 201039Tareb et al., 2013

Effect on the host-microbiota interactions

Postbiotics can affect the immune system, similar to the effects of live probiotics10Taverniti et al., 2011. Cell wall components such as exopolysaccharides (EPS) can share signals with the host immune system and have been shown to play a role in keeping the intestinal environment stable.36Sarkar et al., 201640Patten et al., 201341Gareau et al., 2010 EPS have been shown to provide various health benefits: they can protect the heart, reduce ulcers, act as antioxidants, lower cholesterol levels and reduce tumor growth.1Wegh et al., 201942.44Das et al., 2014 Hongpattarakere et al., 2012 Wang et al., 2014 Besides cell wall components, postbiotics also contain metabolites and soluble factors like antioxidants that can travel to mucosal immune cells and reduce inflammation.45Hoarau et al., 200646De Marco et al., 2018

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1. Wegh CAM, Geerlings SY, Knol J, Roeselers G, Belzer C. Postbiotics and Their Potential Applications in Early Life Nutrition and Beyond. Int J Mol Sci. 2019 Sep 20;20(19). pii: E4673. doi: 10.3390/ijms20194673. Review. PubMed PMID:31547172; PubMed Central PMCID: PMC6801921.

10. Taverniti V, Guglielmetti S. The immunomodulatory properties of probiotic microorganisms beyond their viability (ghost probiotics: proposal of paraprobiotic concept). Genes Nutr. 2011 Aug;6(3):261-74. doi:10.1007/s12263-011-0218-x. Epub 2011 Apr 16. PubMed PMID: 21499799; PubMed Central PMCID: PMC3145061.

35. Piqué N, Berlanga M, Miñana-Galbis D. Health Benefits of Heat-Killed (Tyndallized) Probiotics: An Overview. Int J Mol Sci. 2019 May 23;20(10). pii: E2534. doi: 10.3390/ijms20102534. Review. PubMed PMID: 31126033; PubMed Central PMCID: PMC6566317.

36. Sarkar A, Mandal S. Bifidobacteria-Insight into clinical outcomes and mechanisms of its probiotic action. Microbiol Res. 2016 Nov;192:159-171. doi:10.1016/j.micres.2016.07.001. Epub 2016 Jul 11. Review. PubMed PMID: 27664734.

37. Castro-Bravo N, Wells JM, Margolles A, Ruas-Madiedo P. Interactions of Surface Exopolysaccharides From Bifidobacterium and Lactobacillus Within the Intestinal Environment. Front Microbiol. 2018 Oct 11;9:2426. doi: 10.3389/fmicb.2018.02426. eCollection 2018. Review. PubMed PMID: 30364185; PubMed Central PMCID:PMC6193118.

38. Lebeer S, Vanderleyden J, De Keersmaecker SC. Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens. Nat Rev Microbiol. 2010 Mar;8(3):171-84. doi: 10.1038/nrmicro2297. Review. PubMed PMID: 20157338.

39. Tareb R, Bernardeau M, Gueguen M, Vernoux JP. In vitro characterization of aggregation and adhesion properties of viable and heat-killed forms of two probiotic Lactobacillus strains and interaction with foodborne zoonotic bacteria, especially Campylobacter jejuni. J Med Microbiol. 2013 Apr;62(Pt 4):637-649. doi:10.1099/jmm.0.049965-0. Epub 2013 Jan 17. PubMed PMID: 23329323.

40. Patten DA, Leivers S, Chadha MJ, Maqsood M, Humphreys PN, Laws AP, Collett A. The structure and immunomodulatory activity on intestinal epithelial cells of the EPSs isolated from Lactobacillus helveticus sp. Rosyjski and Lactobacillus acidophilus sp. 5e2. Carbohydr Res. 2014 Jan 30;384:119-27. doi:10.1016/j.carres.2013.12.008. Epub 2013 Dec 12. PubMed PMID: 24394883.

41. Gareau MG, Sherman PM, Walker WA. Probiotics and the gut microbiota in intestinal health and disease. Nat Rev Gastroenterol Hepatol. 2010 Sep;7(9):503-14. doi: 10.1038/nrgastro.2010.117. Epub 2010 Jul 27. Review. PubMed PMID: 20664519; PubMed Central PMCID: PMC4748966.

42. Das D, Baruah R, Goyal A. A food additive with prebiotic properties of an α-d-glucan from lactobacillus plantarum DM5. Int J Biol Macromol. 2014 Aug;69:20-6. doi: 10.1016/j.ijbiomac.2014.05.029. Epub 2014 May 20. PubMed PMID: 24857877.

43. Hongpattarakere, T.; Cherntong, N.; Wichienchot, S.; Kolida, S.; Rastall, R.A. In vitro prebiotic evaluation of exopolysaccharides produced by marine isolated lactic acid bacteria. Carbohyd. Polym. 2012, 87, 846–852.

44. Wang K, Li W, Rui X, Chen X, Jiang M, Dong M. Characterization of a novel exopolysaccharide with antitumor activity from Lactobacillus plantarum 70810. Int J Biol Macromol. 2014 Feb;63:133-9. doi: 10.1016/j.ijbiomac.2013.10.036. Epub 2013 Nov 1. PubMed PMID: 24189393.

45. Hoarau C, Lagaraine C, Martin L, Velge-Roussel F, Lebranchu Y. Supernatant of Bifidobacterium breve induces dendritic cell maturation, activation, and survivalthrough a Toll-like receptor 2 pathway. J Allergy Clin Immunol. 2006Mar;117(3):696-702. Epub 2006 Jan 27. PubMed PMID: 16522473.

46. De Marco S, Sichetti M, Muradyan D, Piccioni M, Traina G, Pagiotti R, Pietrella D. Probiotic Cell-Free Supernatants Exhibited Anti-Inflammatory and Antioxidant Activity on Human Gut Epithelial Cells and Macrophages Stimulated with LPS. Evid Based Complement Alternat Med. 2018 Jul 4;2018:1756308. doi:10.1155/2018/1756308. eCollection 2018. PubMed PMID: 30069221; PubMed Central PMCID: PMC6057331.

Postbiotics in the context of dentistry and L. paracasei GMNL-33

Oral diseases are among the most prevalent of diseases. Worldwide, dental caries (tooth decay) affects 35% of the population and severe periodontitis (gum disease) affects 10.8%.47GBD 201748Peres et al., 2010 These diseases are caused by microorganisms and are the consequence of a dysbiosis,49López-López et al., 2017 which is defined as “an imbalanced interaction either among bacteria in a community or between the microbiome and the host, that is detrimental to the host.”50Lamont et al., 2018

Dental caries

Dental caries can be prevented using several strategies: removing the cariogenic (decay-causing) biofilm, preventing biofilm accumulation with mechanical disruption, using conventional, broad-spectrum antimicrobials, and decreasing the rate of enamel demineralization. However, these strategies have not been successful in some populations that are particularly vulnerable for caries, such as children and the elderly.50Lamont et al., 2018 Broad-spectrum antimicrobials such as chlorhexidine are not very effective on biofilms and can even increase susceptibility to reinfection by pathogens51Guo et al., 2015.Fluoride can limit the demineralization of enamel and promote remineralization, however, it has little effect on the cariogenic biofilm.50Lamont et al., 2018 Thus there is a crucial need for strategies that specifically target the microbial dysbiosis and cariogenic biofilm associated with dental caries.

Periodontitis

Management of gingivitis and chronic periodontitis relies on strategies aimed at eliminating the pathogenic biofilm and controlling the inflammation. They include debridement (removal of the dental plaque and calculus with scaling and root planing), surgical interventions, follow ups by professional dental cleanings, daily self-performed oral hygiene practices and in certain cases, additional therapies such as antibiotics and antimicrobials.52.54Kinane et al., 2017 Gatei et al., 2017 van der Weijden et al., 2005

Though these approaches do temporarily reduce the biofilm and the resulting inflammation, they fail to control the disease in a significant proportion of patients.53.55Gatei et al., 2017 van der Weijden et al., 2005 Quirynen et al., 2000 For these patients, there is a need for additional strategies that specifically target the pathogenic biofilm and modulate immunity in the oral cavity.56.58Teughels et al., 2011 Bustamante et al., 2019 Hoare et al., 2017  

Altogether, postbiotics represent a safe and efficient means of addressing the limitations of the current strategies for preventing and treating dental caries and periodontal diseases.

Illustation Pathogen Inhibition

Lactobacillus paracasei GMLN-33

L. paracasei GMNL-33, also called ADP1, is a postbiotic derived from a tyndallized Lactobacillus paracasei strain. Tyndallisation is a process of inactivating bacterial cells by alternating heat treatments with periods of incubation at lower temperatures.35Piqué et al., 201960Kim et al., 2012

As a heat-killed probiotic, L. paracasei GMNL-33 postbiotic is entirely safe. In addition, L. paracasei GMNL-33 belongs to the genus of Lactobacillus (the largest and most diverse genus within the lactic acid bacteria) and to the Lactobacillus casei group (LCG). The L. paracasei species is Generally Recognized As Safe (GRAS) by the FDA and present on the QPS (qualified presumption of safety) list assembled by the European Food Safety Authority (EFSA).61Hill et al., 2018

Several scientific and clinical studies have shown that the L. paracasei GMNL-33 postbiotic can help inhibit cario- and perio-pathogens (the bacteria associated with caries and periodontitis), leading to its beneficial properties for oral health care.62.65Chuang et al., 2011 Maden et al., 2018 Srinivasan et al., 2017 Ching-Pei et al.: Please contact us 

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35. Piqué N, Berlanga M, Miñana-Galbis D. Health Benefits of Heat-Killed (Tyndallized) Probiotics: An Overview. Int J Mol Sci. 2019 May 23;20(10). pii: E2534. doi: 10.3390/ijms20102534. Review. PubMed PMID: 31126033; PubMed Central PMCID: PMC6566317.

47. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018 Nov10;392(10159):1789-1858. doi: 10.1016/S0140-6736(18)32279-7. Epub 2018 Nov 8. PubMed PMID: 30496104; PubMedCentral PMCID: PMC6227754.

48. Peres MA, Macpherson LMD, Weyant RJ, Daly B, Venturelli R, Mathur MR, Listl S, Celeste RK, Guarnizo-Herreño CC, Kearns C, Benzian H, Allison P, Watt RG. Oral diseases: a global public health challenge. Lancet. 2019 Jul 20;394(10194):249-260. doi: 10.1016/S0140-6736(19)31146-8. Review. Erratum in: Lancet. 2019 Sep 21;394(10203):1010. PubMed PMID: 31327369.

49. López-López A, Camelo-Castillo A, Ferrer MD, Simon-Soro Á, Mira A. Health-Associated Niche Inhabitants as Oral Probiotics: The Case of Streptococcus dentisani. Front Microbiol. 2017 Mar 10;8:379. doi: 10.3389/fmicb.2017.00379. eCollection 2017. PubMed PMID: 28344574; PubMed Central PMCID: PMC5344910.

50. Lamont RJ, Koo H, Hajishengallis G. The oral microbiota: dynamic communities and host interactions. Nat Rev Microbiol. 2018 Dec;16(12):745-759. doi: 10.1038/s41579-018-0089-x. Review. PubMed PMID: 30301974; PubMed Central PMCID: PMC6278837.

51. Guo L, McLean JS, Yang Y, Eckert R, Kaplan CW, Kyme P, Sheikh O, Varnum B, Lux R, Shi W, He X. Precision-guided antimicrobial peptide as a targeted modulator of human microbial ecology. Proc Natl Acad Sci U S A. 2015 Jun 16;112(24):7569-74.doi: 10.1073/pnas.1506207112. Epub 2015 Jun 1. PubMed PMID: 26034276; PubMed Central PMCID: PMC4475959.

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