Abstract
More than 6 billion bacteria and other microorganisms live in the adult oral cavity. As a result of any deleterious effect on this community, some microorganisms will survive better than others, which may trigger pathogenic processes like caries, halitosis, gingivitis or periodontitis. Oral dysbiosis is among the most frequent human health hazards globally. Quality of life of patients deteriorates notably, while treatments are often unpleasant, expensive and irreversible, e.g. tooth loss. In the experiments reported here, we investigated the individual interactions between 8 pathogenic and 8 probiotic strains and a commercially available probiotic product. Almost all pathogens, namely Fusobacterium nucleatum, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Streptococcus mutans, Streptococcus oralis, Streptococcus gordonii, Enterococcus faecalis and Prevotella buccae are pathogens frequently occurring in the oral cavity. The used probiotic strains were Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus delbrueckii, Bifidobacterium thermophilum and two Streptococcus dentisani isolates. Using a modified agar diffusion method, we investigated capability of the probiotic bacteria to prevent the growth of the pathogenic ones in order to identify candidates for future therapeutic treatments. The results indicated successful bacteriocin production, i.e. growth inhibition, against every pathogenic bacterium by at least 5 probiotic strains.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs42977-021-00091-3/MediaObjects/42977_2021_91_Fig1_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs42977-021-00091-3/MediaObjects/42977_2021_91_Fig2_HTML.jpg)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs42977-021-00091-3/MediaObjects/42977_2021_91_Fig3_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs42977-021-00091-3/MediaObjects/42977_2021_91_Fig4_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs42977-021-00091-3/MediaObjects/42977_2021_91_Fig5_HTML.png)
Similar content being viewed by others
References
Anderson AC, Jonas D, Huber I, Karygianni L, Wölber J, Hellwig E, Arweiler N, Vach K, Wittmer A, Al-Ahmad A (2016) Enterococcus faecalis from food, clinical specimens, and oral sites: Prevalence of virulence factors in association with biofilm formation. Front Microbiol. https://doi.org/10.3389/fmicb.2015.01534
Andrade E, dos Santos Pires AC, Soares M, Jan G, de Carvalho AF (2012) Probiotics in dairy fermented products. Probiotics. https://doi.org/10.5772/51939
Anukam KC, Reid G (2007) Probiotics: 100 years (1907-2007) after Elie Metchnikoff ’s observation. Commun Curr Reserach Educ Top Trends Appl Microbiol 466–474
Badet C, Thebaud NB (2008) Ecology of lactobacilli in the oral cavity: a review of literature. Open Microbiol J 2:38–48. https://doi.org/10.2174/1874285800802010038
Balouiri M, Sadiki M, Ibnsouda SK (2016) Methods for in vitro evaluating antimicrobial activity: a review. J Pharm Anal 6:71–79
Banas JA, Fountain TL, Mazurkiewicz JE, Sun K, Margaret Vickerman M (2007) Streptococcus mutans glucan-binding protein-A affects Streptococcus gordonii biofilm architecture. FEMS Microbiol Lett 267:80–88. https://doi.org/10.1111/j.1574-6968.2006.00557.x
Barefoot SF, Klaenhammer TR (1984) Purification and characterization of the Lactobacillus acidophilus bacteriocin lactacin B. Antimicrob Agents Chemother 26:328–334. https://doi.org/10.1128/AAC.26.3.328
Berger D, Rakhamimova A, Pollack A, Loewy Z (2018) Oral biofilms: development, control, and analysis. High-Throughput 7:1–8. https://doi.org/10.3390/ht7030024
Borsanelli AC, Gaetti-Jardim E, Schweitzer CM, Viora L, Busin V, Riggio MP, Dutra IS (2017) Black-pigmented anaerobic bacteria associated with ovine periodontitis. Vet Microbiol 203:271–274. https://doi.org/10.1016/j.vetmic.2017.03.032
Bostanci N, Belibasakis GN (2012) Porphyromonas gingivalis: an invasive and evasive opportunistic oral pathogen. FEMS Microbiol Lett 333:1–9
Bowen WH (2016) Dental caries—not just holes in teeth! A perspective. Mol Oral Microbiol 31:228–233
Brennan CA, Garrett WS (2019) Fusobacterium nucleatum—symbiont, opportunist and oncobacterium. Nat Rev Microbiol 17:156–166
Brown SA, Whiteley M (2007) A novel exclusion mechanism for carbon resource partitioning in Aggregatibacter actinomycetemcomitans. J Bacteriol 189:6407–6414. https://doi.org/10.1128/JB.00554-07
Camelo-Castillo A, Benítez-Páez A, Belda-Ferre P, Cabrera-Rubio R, Mira A (2014) Streptococcus dentisani sp. nov., a novel member of the mitis group. Int J Syst Evol Microbiol 64:60–65. https://doi.org/10.1099/ijs.0.054098-0
Clarke JK (1924) On the bacterial factor in the etiology of dental caries. Br J Exp Pathol 5:141
Cobo F, Rodríguez-Granger J, Sampedro A, Navarro-Marí JM (2017) Infected breast cyst due to Prevotella buccae resistant to metronidazole. Anaerobe 48:177–178. https://doi.org/10.1016/j.anaerobe.2017.08.015
Conrads G, Westenberger J, Lürkens M, Abdelbary MMH (2019) Isolation and bacteriocin-related typing of Streptococcus dentisani. Front Cell Infect Microbiol 9:1–11. https://doi.org/10.3389/fcimb.2019.00110
Cotter PD, Ross RP, Hill C (2013) Bacteriocins-a viable alternative to antibiotics? Nat Rev Microbiol 11:95–105
da Silva-Sabo S, Vitolo M, González JMD, de Oliveira RPS (2014) Overview of Lactobacillus plantarum as a promising bacteriocin producer among lactic acid bacteria. Food Res Int 64:527–536
Dadon Z, Cohen A, Szterenlicht YM, Assous MV, Barzilay Y, Raveh-Brawer D, Yinnon AM, Munter G (2017) Spondylodiskitis and endocarditis due to Streptococcus gordonii. Ann Clin Microbiol Antimicrob 16:4–7. https://doi.org/10.1186/s12941-017-0243-8
De Giani A, Bovio F, Forcella M, Fusi P, Sello G, Di Gennaro P (2019) Identification of a bacteriocin-like compound from Lactobacillus plantarum with antimicrobial activity and effects on normal and cancerogenic human intestinal cells. AMB Express. https://doi.org/10.1186/s13568-019-0813-6
Dige I, Nyengaard JR, Kilian M, Nyvad B (2009) Application of stereological principles for quantification of bacteria in intact dental biofilms. Oral Microbiol Immunol 24:69–75. https://doi.org/10.1111/j.1399-302X.2008.00482.x
Distel JW, Hatton JF, Gillespie MJ (2002) Biofilm formation in medicated root canals. J Endod 28:689–693. https://doi.org/10.1097/00004770-200210000-00003
Do T, Jolley KA, Maiden CJ, Gilbert SC, Clark D, Wade WG, Beighton D (2009) Population structure of Streptococcus oralis. Microbiology 155:2593–2602. https://doi.org/10.1099/mic.0.027284-0
Dobson A, Cotter PD, Paul Ross R, Hill C (2012) Bacteriocin production: a probiotic trait? Appl Environ Microbiol 78:1–6
Ebbers M, Lübcke PM, Volzke J, Kriebel K, Hieke C, Engelmann R, Lang H, Kreikemeyer B, Müller-Hilke B (2018) Interplay between P. gingivalis, F. nucleatum and A. actinomycetemcomitans in murine alveolar bone loss, arthritis onset and progression. Sci Rep 8:1–10. https://doi.org/10.1038/s41598-018-33129-z
Et P, Mpa M (2014) JBR J Interdiscip Enterococcus faecalis Oral Infect 3:1–5
Fine DH, Markowitz K, Furgang D, Velliyagounder K (2010) Aggregatibacter actinomycetemcomitans as an early colonizer of oral tissues: Epithelium as a reservoir? J Clin Microbiol 48:4464–4473. https://doi.org/10.1128/JCM.00964-10
Fine DH, Patil AG, Velusamy SK (2019) Aggregatibacter actinomycetemcomitans (Aa) under the Radar: Myths and misunderstandings of AA and its role in aggressive periodontitis. Front Immunol 10
Fine HD, Karched M, Furgang D, Sampathkumar V, Velusamy S, Godboley D (2015) Colonization and presistence of labeled and foreign strains of Aa inoculated into the mouths of rhesus monkeys. J Oral Biol 136:554–561. https://doi.org/10.1016/j.ygyno.2014.12.035.Pharmacologic
Forssten SD, Björklund M, Ouwehand AC (2010) Streptococcus mutans, caries and simulation models. Nutrients 2:290–298
Gaspar C, Donders GG, Palmeira-de-Oliveira R, Queiroz JA, Tomaz C, Martinez-de-Oliveira J, Palmeira-de-Oliveira A (2018) Bacteriocin production of the probiotic Lactobacillus acidophilus KS400. AMB Express 8:153. https://doi.org/10.1186/s13568-018-0679-z
Hajishengallis G, Lamont RJ (2014) Breaking bad: manipulation of the host response by Porphyromonas gingivalis. Eur J Immunol 44:328–338. https://doi.org/10.1002/eji.201344202
Han YW (2015) Fusobacterium nucleatum: a commensal-turned pathogen. Curr Opin Microbiol 23:141–147
Hata S, Mayanagi H (2003) Acid diffusion through extracellular polysaccharides produced by various mutants of Streptococcus mutans. Arch Oral Biol 48:431–438. https://doi.org/10.1016/S0003-9969(03)00032-3
Holt S, Kesavalu L, Walker S, Genco CA (1999) Virulence factors of P.gingivalis. Periodontol 2000(20):168–238
How KY, Song KP, Chan KG (2016) Porphyromonas gingivalis: an overview of periodontopathic pathogen below the gum line. Front Microbiol 7:1–14
Huot E, Petitdemange H (1996) Tween 80 effect on bacteriocin synthesis by Lactococcus. Lett Appl Microbiol 22:307–310
Jakubovics NS, Palmer RJ Jr (2013) Oral Microbial ecology current research and new perspectives. Caister Academic Press, Norfolk, UK
Jeong YJ, Moon GS (2015) Antilisterial bacteriocin from Lactobacillus rhamnosus CJNU 0519 presenting a narrow antimicrobial spectrum. Korean J Food Sci Anim Resour 35:137–142. https://doi.org/10.5851/kosfa.2015.35.1.137
Karayasheva D, Radeva E (2017) Importance of enterococci (Enterococcus faecalis) for dental medicine ? Microbiological characterization, prevalence and resistance. Int J Sci Res 6:1970–1973. https://doi.org/10.21275/art20175821
Kato H, Taguchi Y, Tominaga K, Umeda M, Tanaka A (2014) Porphyromonas gingivalis LPS inhibits osteoblastic differentiation and promotes pro-inflammatory cytokine production in human periodontal ligament stem cells. Arch Oral Biol 59:167–175. https://doi.org/10.1016/j.archoralbio.2013.11.008
Kim N, Yun M, Oh YJ, Choi HJ (2018) Mind-altering with the gut: modulation of the gut-brain axis with probiotics. J Microbiol 56:172–182. https://doi.org/10.1007/s12275-018-8032-4
Kouidhi B, Zmantar T, Mahdouani K, Hentati H, Bakhrouf A (2011) Antibiotic resistance and adhesion properties of oral Enterococci associated to dental caries. BMC Microbiol. https://doi.org/10.1186/1471-2180-11-155
Krespi YP, Shrime MG, Kacker A (2006) The relationship between oral malodor and volatile sulfur compound-producing bacteria. Otolaryngol Head Neck Surg 135:671–676
Lemos JA, Burne RA (2008) A model of efficiency: stress tolerance by Streptococcus mutans. Microbiology 154:3247–3255
Lemos JA, Palmer SR, Zeng L, Wen ZT, Kajfasz JK, Freires IA, Abranches J, Brady LJ (2019) The biology of Streptococcus mutans. Microbiol Spectr 7:1–18. https://doi.org/10.1128/microbiolspec.gpp3-0051-2018
López-López A, Camelo-Castillo A, Ferrer MD, Simon-Soro Á, Mira A (2017) Health-associated niche inhabitants as oral probiotics: the case of Streptococcus dentisani. Front Microbiol 8:1–3. https://doi.org/10.3389/fmicb.2017.00379
Marcotte H, Lavoie MC (1998) Oral microbial ecology and the role of salivary immunoglobulin A. Microbiol Mol Biol Rev 62:71–109
Martinez FAC, Balciunas EM, Converti A, Cotter PD, de Souza Oliveira RP (2013) Bacteriocin production by Bifidobacterium spp. A Rev Biotechnol Adv 31:482–488. https://doi.org/10.1016/j.biotechadv.2013.01.010
Md Sidek NL, Halim M, Tan JS, Abbasiliasi S, Mustafa S, Ariff AB (2018) Stability of bacteriocin-like inhibitory substance (BLIS) produced by Pediococcus acidilactici kp10 at different extreme conditions. Biomed Res Int. https://doi.org/10.1155/2018/5973484
Metwalli KH, Khan SA, Krom BP, Jabra-Rizk MA (2013) Streptococcus mutans, Candida albicans, and the human mouth: a sticky situation. PLoS Pathog. https://doi.org/10.1371/journal.ppat.1003616
Miller K, Treloar T, Guelmann M, Rody WJ, Shaddox LM (2018) Clinical characteristics of localized aggressive periodontitis in primary dentition. J Clin Pediatr Dent 42:95–102. https://doi.org/10.17796/1053-4628-42.2.3
Müller E, Radler F (1993) Caseicin, a bacteriocin from Lactobacillus casei. Folia Microbiol (praha) 38:441–446. https://doi.org/10.1007/BF02814392
Pan H, Guo R, Ju Y, Wang Q, Zhu J, Xie Y, Zheng Y, Li T, Liu Z, Lu L, Li F, Tong B, Xiao L, Xu X, Leung EL-H, Li R, Yang H, Wang J, Zhou H, Jia H, Liu L (2019) A single bacterium restores the microbiome dysbiosis to protect bones from destruction in a rat model of rheumatoid arthritis. Microbiome 7:1–11. https://doi.org/10.1186/s40168-019-0719-1
Park J, Shokeen B, Haake SK, Lux R (2016) Characterization of Fusobacterium nucleatum ATCC 23726 adhesins involved in strain-specific attachment to Porphyromonas gingivalis. Int J Oral Sci 8:138–144. https://doi.org/10.1038/ijos.2016.27
Petersen PE, Ogawa H (2012) The global burden of periodontal disease: Towards integration with chronic disease prevention and control. Periodontology 2000 60(1):15–39. https://doi.org/10.1111/j.1600-0757.2011.00425.x
Praveen T, Kotrashetti VS, Pattanshetty S, Hosmani J V, Babji D, Ingalagi P (2018) Detection of different Prevotella species from deep dentinal caries of primary teeth—a culture and biochemical study. J Adv Clin Res Insights 5:65–68. https://doi.org/10.15713/ins.jcri.213
Raja M, Ummer F, Dhivakar CP (2014) Aggregatibacter actinomycetemcomitans—a tooth killer. J Clin Diagn Res 8:13–17
Reitermayer D, Kafka TA, Lenz CA, Vogel RF (2018) Interrelation between Tween and the membrane properties and high pressure tolerance of Lactobacillus plantarum. BMC Microbiol 18:1–14. https://doi.org/10.1186/s12866-018-1203-y
Shungu D, Valiant M, Tutlane V (1983) GELRITE as an agar substitute in bacteriological media. Appl Environ Microbiol 46:840–845
Simova ED, Beshkova DM, Angelov MP, Dimitrov ZP (2008) Bacteriocin production by strain Lactobacillus delbrueckii ssp. bulgaricus BB18 during continuous prefermentation of yogurt starter culture and subsequent batch coagulation of milk. J Ind Microbiol Biotechnol 35:559–567. https://doi.org/10.1007/s10295-008-0317-x
Ullah N, Wang X, Wu J, Guo Y, Ge H, Li T, Khan S, Li Z, Feng X (2017) Purification and primary characterization of a novel bacteriocin, LiN333, from Lactobacillus casei, an isolate from a Chinese fermented food. LWT Food Sci Technol 84:867–875. https://doi.org/10.1016/j.lwt.2017.04.056
Wang B, Kuramitsu HK (2005) Interactions between oral bacteria: Inhib Soc 71:354–362. https://doi.org/10.1128/AEM.71.1.354
Wilkins JC, Beighton D, Homer KA (2003) Effect of acidic pH on expression of surface-associated proteins of Streptococcus oralis. Appl Environ Microbiol 69:5290–5296. https://doi.org/10.1128/AEM.69.9.5290-5296.2003
Zambon JJ (1985) Actinobacillus actinomycetemcomitans in human periodontal disease
Zhou B, Zhang D (2018) Antibacterial effects of bacteriocins isolated from Lactobacillus rhamnosus (ATCC 53103) in a rabbit model of knee implant infection. Exp Ther Med 15:2985–2989. https://doi.org/10.3892/etm.2018.5790
Acknowledgements
We thank University of Szeged, Institute of Clinical Microbiology and Goodwill Pharma Ltd. for providing strains and the probiotic preparation for this study.
Funding
This study has been supported in part by the Hungarian National Research, Development and Innovation Fund projects GINOP-2.3.2-15-2016-00011, GINOP-2.2.1-15-2017-00081, GINOP-2.2.1-15-2017-00033 and EFOP-3.6.2-16-2017-00010. ZB received support from the Hungarian NKFIH fund FK123902.
Author information
Authors and Affiliations
Contributions
NG, with the help from OS, designed and performed the experiments and contributed to the evaluation of the data. KLK conceived the project and participated in its design. NG, OS, ZB and KLK drafted the manuscript. All the authors have read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Rights and permissions
About this article
Cite this article
Gönczi, N.N., Strang, O., Bagi, Z. et al. Interactions between probiotic and oral pathogenic strains. BIOLOGIA FUTURA 72, 461–471 (2021). https://doi.org/10.1007/s42977-021-00091-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s42977-021-00091-3