Beyond probiotics:

postbiotics

What are probiotics, prebiotics, synbiotics & postbiotics?

The term “biotic” originates from the Greek word biōtikós that means “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

In 1953, the same year as the discovery of the double helix structure of DNA, the word “probiotics” was used for the first time to introduce the “essential active substances for the healthy development of life.”2Gasbarrini G. et al., 2016 Currently, a probiotic is defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.3Hill C. et al., 2014

A prebiotic is a “substrate that is selectively utilized by host microorganisms conferring a health benefit.4Gibson 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.5FAO/WHO, 20016FAO/WHO, 2002

There is no global consensus yet on the definition of the term “postbiotic,” as it is fairly new in the field of biotics. The best definition attempt is that a postbiotic is a bioactive compound produced during a fermentation process that supports health and/or wellbeing,7Collado et al., 2019 in a direct or indirect way.”8Tsilingiri et al., 2013 Importantly, the viability of the microorganism underlying the effect is no longer required. Thus, non-viable, inactivated or heat-killed microbial cells (also called parabiotics), microbial metabolites (proteins, lipids, carbohydrates, vitamins, organic acids), cell wall components, or other complex molecules from the bacterial extracellular matrix can be considered as postbiotics.9.13George 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. Gasbarrini G, Bonvicini F, Gramenzi A. Probiotics History. J Clin Gastroenterol. 2016 Nov/Dec;50 Suppl 2, Proceedings from the 8th Probiotics,Prebiotics & New Foods for Microbiota and Human Health meeting held in Rome, Italy on September 13-15, 2015:S116-S119. PubMed PMID: 27741152.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

How do postbiotics differ from probiotics and prebiotics and what is their benefit?

The majority of probiotics are lactic acid bacteria (LAB) such as Lactobacillus or Bifidobacterium species. They are Generally Recognized As Safe (GRAS) by the FDA14O’Toole et al., 2017 and are used for a variety of applications ranging from food industry to clinical practice.3Hill et al., 201414O’Toole et al., 201715Wilkins et al., 2017 However, there are growing concerns in the scientific and medical communities regarding the safety of probiotic use in vulnerable populations, particularly younger children and adults with underlying conditions.16.18Goldstein et al., 2015 Doron et al., 2015 Ohishi et al., 2010

One of the main concerns is probiotic translocation from the gut—or more generally from the area of application—to the systemic circulation to provoke bacteremia.19.26Barraud 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 This concern has been dramatically validated by Yelin et al, which demonstrated that probiotics can directly cause bacteremia and adaptively evolve within critically ill patients.27Yelin et al., 2019 Another issue is the potential acquisition and transfer of antibiotic resistance genes to pathogenic bacteria via horizontal gene transfer.28Wong et al., 201529Aceti et al., 2018 In addition, specific probiotic strains can express putative virulence factors leading to cytotoxic effects30Rowan et al., 2001 or replace existing commensal beneficial bacteria.

Most prebiotics are carbohydrate-based31Sanders et al., 2019 and include oligosaccharides such as short-chain galactooligosaccharides (scGOS) and long-chain fructooligosaccharides (lcFOS)32.34Giovannini et al., 2014 Vandenplas et al., 2015 Sierra et al., 2014 as well as various dietary fibers. Prebiotics are supposed to selectively modulate the microbiota by promoting the growth of certain species in order to confer a health benefit.4Gibson et al., 2017 However, microbiome sequencing studies have revealed that the outcomes of prebiotic administration are much more complex35Hutkins et al., 2016, as unexpected or yet unidentified members of the microbiota can be enriched directly or by cross-feeding.36.38Trompette et al., 2014 Holscher et al., 2015 Salonen et al., 2014

Postbiotics appear to address most of these issues and limitations. Notably, they are safer than probiotics since they can be dosed to optimal efficacy without the risk of bacterial growth.39de Almada et al., 2016

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3. 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.

4. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

27. Yelin I, Flett KB, Merakou C, Mehrotra P, Stam J, Snesrud E, Hinkle M, Lesho E, McGann P, McAdam AJ, Sandora TJ, Kishony R, Priebe GP. Genomic and epidemiological evidence of bacterial transmission from probiotic capsule to blood in ICU patients. Nat Med. 2019 Nov;25(11):1728-1732. doi:10.1038/s41591-019-0626-9. Epub 2019 Nov 7. PubMed PMID: 31700189; PubMed Central PMCID: PMC6980696.

28. 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.

29. 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.

30. 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.

31. 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.

32. Giovannini M, Verduci E, Gregori D, Ballali S, Soldi S, Ghisleni D, Riva E; PLAGOS Trial Study Group. Prebiotic effect of an infant formula supplemented with galacto-oligosaccharides: randomized multicenter trial. J Am Coll Nutr.2014;33(5):385-93.doi:10.1080/07315724.2013.878232. Epub 2014 Oct 10. PubMed PMID: 25302927.

33. Vandenplas Y, Zakharova I, Dmitrieva Y. Oligosaccharides in infant formula: more evidence to validate the role of prebiotics. Br J Nutr. 2015 May 14;113(9):1339-44. doi: 10.1017/S0007114515000823. Review. PubMed PMID: 25989994.

34. Sierra C, Bernal MJ, Blasco J, Martínez R, Dalmau J, Ortuño I, Espín B, Vasallo MI, Gil D, Vidal ML, Infante D, Leis R, Maldonado J, Moreno JM, Román E. Prebiotic effect during the first year of life in healthy infants fed formula containing GOS as the only prebiotic: a multicentre, randomised, double-blind and placebo-controlled trial. Eur J Nutr. 2015 Feb;54(1):89-99. doi:10.1007/s00394-014-0689-9. Epub 2014 Mar 27. PubMed PMID: 24671237; PubMed Central PMCID: PMC4303717.

35. 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.

36. 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.

37. 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.

38. 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.

39. 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, bacterial viability is not required for efficacy40Piqué et al., 2019 and postbiotics can mimic the mechanisms of action of probiotics through the components of microbial cells and metabolites. Postbiotics mainly act at two levels:

Effect on microbial community interactions

Postbiotics can inhibit pathogens through the effect of bacteriocins as well as organic acids and can prevent pathogen adhesion, invasion and biofilm formation.1Wegh et al., 201940Piqué et al., 2019

Competition with gastrointestinal pathogens for adhesion sites has been well documented in postbiotics such as heat-killed cells.41.44Canducci et al., 2000 Aiba et al., 2017 Chauvière et al., 1992 Moyen et al., 1986 Cell wall components such as exopolysaccharides (EPS) isolated from LAB possess anti-adhesive properties against pathogens, notably through the formation of a protective film.40Piqué et al., 201945Sarkar et al., 201646Castro-Bravo et al., 2018 Surface layer proteins (SLP) can also contribute to the co-aggregation of pathogenic bacteria.47Lebeer et al., 201048Tareb et al., 2013

Cell-free supernatants contain a wide range of antibacterial compounds like lactic acid and hydrogen peroxide40Piqué et al., 201949Mariam et al., 2014 50Lukic et al., 2017. They also contain antimicrobial peptides (AMPs) such as bacteriocins, which are ribosomally synthesized AMPs. Bacteriocins have well-described bacteriostatic or bactericidal properties.51.54Kareem et al., 2014 Ooi et al., 2015 Dobson et al., 2011 do Carmo et al., 2018 Other interesting properties of bacteriocins are a good tolerance to pH (ranging from 3 to 10) and thermal stability, which allows bacteriocins to retain their biological activity in heat-killed cells.45Sarkar et al., 2016

Effect on host-microbiota interactions

Postbiotics have immunomodulatory effects similar to those found in living probiotics.11Taverniti et al., 2011 LAB can elicit IL-12 production, which promotes innate immunity.55Arai et al., 2018 Interestingly, postbiotics such as heat-killed bacteria induced even higher levels of IL-12 than did live bacteria.56Izumo et al., 201157Sashihara et al., 2007 Lactobacillus paracasei appears to have the highest capacity to induce IL-12 secretion compared with Lactobacillus reuteri, Lactobacillus casei and Lactobacillus plantarum.55Arai et al., 2018 Other experiments with postbiotics originating from Bifidobacterium breve and Streptococcus thermophilus induced high IL-10 secretion through TLR-2, indicating immune regulatory functions.58Hoarau et al., 2006

In addition, cell wall components such as lipoteichoic acids and peptidoglycans are involved in the immunomodulatory properties of postbiotics.59Lee et al., 201360Vinogradov et al., 2016 Lipoteichoic acids have been shown to be IL-12 inducers61Kolling et al., 2018 while peptidoglycans can inhibit the release of inflammatory cytokines.62Wu et al., 2015 EPS and SLP are also engaged in the crosstalk with the host immune system and have been shown to play a role in intestinal homeostasis.45Sarkar et al., 201663Patten et al., 201364Gareau et al., 2010 Various health benefits of EPS have been described, including cardio-protective, antiulcer, antioxidant, hypocholesterolemic and anti-proliferative effects.1Wegh et al., 201965.67Das et al., 2014 Hongpattarakere et al., 2012 Wang et al., 2014 Finally, cell-free supernatants contain metabolites and soluble factors that can interact with mucosal immune cells and possess anti-inflammatory and antioxidant activity.58Hoarau et al., 200668De Marco et al., 2018

Expand bibliographyClose bibliography

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.

11. 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.

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Postbiotics in the context of dentistry

Oral diseases are among the most prevalent diseases worldwide. Dental caries (tooth decay) and severe periodontitis (gum disease) affect 35% and 10.8% of the world’s population, respectively.69GBD 201770Peres et al., 2010 These diseases are caused by microorganisms and are the consequence of a dysbiosis.71López-López et al., 2017

Dental caries

The etiology of caries is polymicrobial.71López-López et al., 2017 Streptococci (especially Streptococcus mutans) and Lactobacilli are well known for their association with caries, but recent microbiome analyses have highlighted the involvement of other pathogens such as non-streptococcal bacteria. 72.76Lamont et al., 2018 Hajishengallis et al., 2016 Mira et al., 2017 Tanner et al., 2018 Eriksson et al., 2017 Dental caries are driven by diet-microbiota interactions that can lead to an acidification of the ecosystem, followed by dysbiosis, a subsequent cariogenic biofilm, and ultimately to mineralized tooth tissue destruction. 72Lamont et al., 201877.81Bowen et al., 2017 Kilian et al., 2016 Marsh et al., 2017 Takahashi et al., 2011 Pitts et al., 2017 

The prevention of dental caries consists of removing existing cariogenic biofilm, preventing biofilm accumulation through mechanical disruption or conventional, broad-spectrum antimicrobial approaches, and decreasing the rate of enamel demineralization.

However, such approaches have not proved successful in populations particularly vulnerable to caries such as children and elderly who have dexterity issues preventing optimal tooth brushing. 72Lamont et al., 2018  In addition, some areas like the sulcal and interproximal surfaces are difficult to access. 72Lamont et al., 2018  Wide-spectrum antimicrobials such as chlorhexidine (CHX) have very limited efficacy on biofilms, and antiseptics such as hydrogen peroxide also exhibit limited antimicrobial activity on biofilms even at high concentrations. 82Liu et al., 2018  Furthermore, they can increase susceptibility to reinfection by pathogens.83Guo et al., 2015  Recent studies have even shown that CHX can induce further perturbation of the commensal microbiota84Chatzigiannidou et al., 2020  and induce a shift to an acidic environment that is beneficial to dental caries.85Bescos et al., 2020  As for fluoride, it can limit the enamel demineralization and promote remineralization, however, its effect on the cariogenic biofilm is limited. 72Lamont et al., 2018  Thus, there is a crucial need for strategies specifically targeting the caries-associated microbial dysbiosis and the cariogenic biofilm.

Periodontitis

Periodontal diseases encompass various inflammatory disorders of the tooth-supporting tissues, which include the gingiva, periodontal ligament, and alveolar bone (collectively known as the periodontium), and range from gingivitis to chronic periodontitis.86Kinane et al., 201787Hajishengallis et al., 2015   One of the key factors in the etiology of periodontitis is an active bacterial subversion of the host immune response, leading to tissue destruction and enabling pathogen persistence.87Hajishengallis et al., 2015  This leads to the maintenance of a dysbiotic inflammation and, ultimately, tooth loss.88Darveau et al., 201289Hajishengallis et al., 2011  In addition, periodontitis has been associated with a wide range of systemic diseases including cardiovascular disease, diabetes mellitus, and adverse pregnancy outcomes.90.95Monsarrat et al., 2016 Beck et al., 2019 Kumar et al., 2017 Bui et al., 2019 Hand et al., 2016 Potempa et al., 2017 

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 prophylaxis, daily self-performed oral hygiene practices, and in certain cases, adjunctive therapies such as systemic antibiotics and antimicrobials.86Kinane et al., 201796Gatei et al., 201797van der Weijden et al., 2005   

However, while these approaches lead to a temporary reduction of the biofilm and the subsequent inflammation, they fail to control the disease in a significant proportion of patients.96.98Gatei et al., 2017 van der Weijden et al., 2005 Quirynen et al., 2000 In this context, alternative adjunctive strategies that specifically target the pathogenic biofilm and modulate immunity in the oral cavity are needed.99.101Teughels et al., 2011 Bustamante et al., 2019 Hoare et al., 2017  

Altogether, postbiotics represent a safe and efficient opportunity to address the limitations of current preventive and treatment strategies linked to dental caries and periodontal disease management.

Lactobacillus paracasei GMLN-33

Tyndallized L. paracasei GMNL-33, also called ADP1, is a postbiotic derived from a Lactobacillus paracasei strain. The tyndallization is a process by which inactivation is obtained through the combination of heat treatments with incubation periods at lower temperatures.40Piqué et al., 2019102Kim et al., 2012  L. paracasei GMNL-33 belongs to the genus of Lactobacillus and to the Lactobacillus casei group (LCG). L. paracasei species are generally recognized as safe by the FDA and present on the QPS list assembled by the EFSA103Hill et al., 2018  and are already being used as probiotics in various clinical and industrial applications.

Several scientific and clinical studies have shown that tyndallized L. paracasei GMNL-33 could inhibit cario- and perio-pathogens, leading to its beneficial properties for oral health care:

In-vitro inhibition of cario- and perio-pathogens

In co-culture experiments, after 1 hour, tyndallized L. paracasei GMNL-33 inhibited 60 to 70% of the growth of P. gingivalis and C. periodontitii, and 50% of the growth of P. intermedia and a clinical specimen sampling of subgingival plaque. After 3 hours, 80% of the growth of P. gingivalis and C. periodontitii was inhibited.

In-vivo inhibition of the cario-pathogen S. mutans

Seventy-eight subjects were involved in a double-blind, randomized, placebo-controlled study. A test group (n=42) and a control group (n=36) respectively took a tyndallized L. paracasei GMNL-33 tablet (3×108 cells/tablet) and a placebo oral tablet three times per day for 2 weeks. Bacterial counts of salivary S. mutans, lactobacilli, and salivary buffer capacity were measured with chair-side kits at the beginning (T1) and completion (T2) of medication and 2 weeks after medication (T3). A significant count reduction in salivary S. mutans was detected between T2 and T3 (p=0.016).104Chuang et al., 2011 

In a study involving a group of 20 children aged 13–15 years old, a 73.5% reduction of S. mutans counts was observed after 6 weeks’ use of a toothpaste containing tyndallized L. paracasei GMNL-33.105Maden et al., 2018  Another study involving a small group of children (mean age 10.2 years) showed that a toothpaste containing tyndallized L. paracasei GMNL-33 significantly reduced the S. mutans monospecies biofilm growth up to 45 minutes after brushing and being immediately exposed to 40% sucrose load.106Srinivasan et al., 2017 

In-vivo inhibition of the perio-pathogen P. gingivalis

Forty subjects were involved in a double-blind, randomized, placebo-controlled trial. A test group (n=20) and a control group (n=20) respectively took a tyndallized L. paracasei GMNL-33 tablet (3×108 cells/tablet) and a placebo oral tablet three times per day for 8 weeks. Total oral bacteria count, periodontal pathogens (P. gingivalis & P. intermedia) counts were examined at the beginning of the test, at 4 weeks and at 8 weeks after enrollment.

After 8 weeks, the total oral bacterial counts decreased significantly in the test group compared to the control group. The growth of P. gingivalis and P. intermedia was almost completely inhibited in the test group (95% of patients) after 4 weeks.107Ching-Pei et al., 2007: Please contact us 

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