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. 2022 Mar 25;12:806463. doi: 10.3389/fcimb.2022.806463

Table 1.

The regulatory effects of known probiotic species promoting periodontal health.

Genus/type Species Regulate immune responses Regulate periodontal microbiota
Lactobacillus Lactobacillus acidophilus

  1. Reduce Porphyromonas gingivalis-induced pro-inflammatory IL-1β and IL-6/8 production in KB cells (in vitro experiment) (Zhao et al., 2012)

  2. Reduce the Fusobacterium nucleatum-induced pro-inflammatory IL-6/8 production in KB and HOK cells (in vitro experiment) (Kang et al., 2011; Ding et al., 2021)

  3. Antagonize the regulatory effect on the proliferation and apoptosis stimulated by P. gingivalis (in vitro experiment) (Zhao et al., 2019)

  1. Inhibit the growth of P. gingivalis (in vitro experiment) (Zhao et al., 2011)

  2. Co-aggregate with F. nucleatum to interfere with adhesion and invasion (in vitro experiment) (Ding et al., 2021)

  3. Downregulate the virulence-associated factors (mfa1, fimA, kgp, rgpA, and luxS) of P. gingivalis (in vitro experiment) (Ishikawa et al., 2020)

  4. Downregulate the adhesion-associated factors (fap2) of F. nucleatum (in vitro experiment) (Ding et al., 2021)

  5. Downregulate the virulence-associated factors (LtxA, CdtB, dspB, and katA) of Aggregatibacter actinomycetemcomitans (in vitro experiment) (Ishikawa et al., 2021)

  6. Degrade A. actinomycetemcomitans biofilms by producing enzymes such as lipase (in vitro experiment) (Jaffar et al., 2016)
Lactobacillus brevis Produce arginine deiminase to reduce the level of pro-inflammatory factors (TNF-α, IL-1β, IL-6, and IL-17) (animal experiment) (Maekawa and Hajishengallis, 2014)

  1. Promote a higher ratio between aerobic and anaerobic bacteria in ligature-associated microbiota (animal experiment) (Maekawa and Hajishengallis, 2014)

  2. Inhibit A. actinomycetemcomitans in saliva (clinical trial) (Shah and Gujjari, 2017)

  3. Inhibit the growth and biofilm formation of Prevotella melaninogenica (in vitro experiment) (Shah and Gujjari, 2017)
Lactobacillus casei Reduce the F. nucleatum-induced pro-inflammatory IL-6 production in oral epithelial cells (in vitro experiment) (Kang et al., 2011)

  1. Reduce the abundance of P. gingivalis, A. actinomycetemcomitans, and P. intermedia in subgingival plaque (clinical trial) (Imran et al., 2015)

  2. Degrade A. actinomycetemcomitans biofilms by producing enzymes such as lipase (in vitro experiment) (Jaffar et al., 2016)
Lactobacillus fermentum Reduce the F. nucleatum-induced pro-inflammatory IL-6 production in oral epithelial cells (in vitro experiment) (Kang et al., 2011)

  1. Degrade A. actinomycetemcomitans biofilms by producing enzymes such as lipase (in vitro experiment) (Jaffar et al., 2016)

  2. Inhibit the growth of P. gingivalis, P. intermedia, and A. actinomycetemcomitans (in vitro experiment) (Terai et al., 2015)
Lactobacillus gasseri

  1. Raise the level of mBD14 mRNA in gingiva, tongue, and saliva (animal experiment) (Kobayashi et al., 2017)

  2. Decrease the mRNA levels of IL-6 and TNF-α in gingiva infected by P. gingivalis (animal experiment) (Kobayashi et al., 2017)

  1. Reduce the expression of LtxA and CdtB exotoxins by A. actinomycetemcomitans (in vitro experiment) (Nissen et al., 2014)

  2. Inhibit the growth of P. gingivalis and P. intermedia (in vitro experiment) (Terai et al., 2015)

  3. Decrease the colonization of P. gingivalis in gingiva (animal experiment) (Kobayashi et al., 2017)
Lactobacillus reuteri

  1. Reduce the F. nucleatum-induced pro-inflammatory cytokine IL-6 production in KB cells (in vitro experiment) (Kang et al., 2011)

  2. Raise the hemocyte density in Galleria mellonella infected by P. gingivalis, upregulating immune responses (animal experiment) (Geraldo et al., 2020; Santos et al., 2020)

  3. Reduce the level of MMP-8 and increase the level of TIMP-1 (clinical trial) (Ince et al., 2015)

  4. Inhibit the expression of pro-inflammatory factors (TNF-α, IL-1β, and IL-17) (clinical trial) (Szkaradkiewicz et al., 2014)

  1. Inhibit the growth of P. gingivalis, P. intermedia, A. actinomycetemcomitans, and F. nucleatum depending on B12, presence of anaerobiosis, and substrate glycerol (in vitro experiment) (Geraldo et al., 2020; Santos et al., 2020; Jansen et al., 2021)

  2. Inhibit P. gingivalis in saliva, supragingival plaque and subgingival plaque, and P. intermedia in saliva (clinical trial) (Invernici et al., 2018)

  3. Reduce the load of P. gingivalis in peri-implant mucositis (clinical trial) (Galofré et al., 2018)
Lactobacillus rhamnosus Reduce the number of TRAP-positive cells and infiltrating inflammatory cells (animal experiment) (Gatej et al., 2018)

  1. Inhibit the growth of P. gingivalis, A. actinomycetemcomitans, and F. nucleatum (in vitro experiment) (Moman et al., 2020)

  2. Reduce the biofilm biomass and viable counts in biofilm of A. actinomycetemcomitans by releasing postbiotics (in vitro experiment) (Ishikawa et al., 2021).

  3. Downregulate the virulence-associated factors (LtxA, CdtB, dspB, and katA) of A. actinomycetemcomitans (in vitro experiment) (Ishikawa et al., 2021)
Lactobacillus salivarius –

  1. Inhibit A. actinomycetemcomitans in saliva and GCF (clinical trial) (Sajedinejad et al., 2017)

  2. Reduce the expression of LtxA and CdtB exotoxins by A. actinomycetemcomitans (in vitro experiment) (Nissen et al., 2014)
Lactobacillus johnsonii, Lactobacillus fructosum, Lactobacillus delbrueckii subsp. casei – Degrade A. actinomycetemcomitans biofilms by producing enzymes such as lipase (in vitro experiment) (Jaffar et al., 2016)
Bifidobacterium Bifidobacterium animalis subsp. lactis

  1. Increase the expression of anti-inflammatory factors (IL-10, TGF-β1, OPG, and β-defensins) and reduce the expression of pro-inflammatory factors (TNF-α, IL-1β, IL-6, CINC, and RANKL) in gingival tissues of experimental periodontitis (animal experiment) (Oliveira et al., 2017; Ricoldi et al., 2017; Silva et al., 2021)

  2. Reduce the expression of IL-1β and the ratio of RANKL/OPG in gingival tissues of rats with periodontitis and metabolic syndrome (animal experiment) (Silva et al., 2021)

  3. Reduce IL-1β in GCF (clinical trial) (Kuru et al., 2017)

  4. Raise the expression of β-defensin, TLR4, and CD4 in gingiva (clinical trial) (Invernici et al., 2020)

  1. Inhibit the growth of P. gingivalis, P. intermedia, A. actinomycetemcomitans, and F. nucleatum (in vitro experiment) (Invernici et al., 2020)

  2. Reduce the adhesion of P. gingivalis to buccal epithelial cells (in vitro experiment) (Invernici et al., 2020)

  3. Antagonize the biofilm formation of F. nucleatum and P. gingivalis (in vitro experiment) (Argandoña Valdez et al., 2021)

  4. Change the ratio between aerobic and anaerobic bacteria and the proportion of subgingival community in animal models (animal experiment) (Oliveira et al., 2017; Ricoldi et al., 2017)

  5. Reduce the level of P. gingivalis, Treponema denticola, Fusobacterium nucleatum vincentii, and A. actinomycetemcomitans in deep periodontal pockets, saliva, and dental plaque (clinical trial) (Alanzi et al., 2018; Invernici et al., 2018)
Streptococcus Streptococcus salivarius Inhibit the expression of IL-6 and IL-8 induced by P. gingivalis, A. actinomycetemcomitans, and F. nucleatum in gingival fibroblasts (in vitro experiment) (Adam et al., 2011; MacDonald et al., 2021).

  1. Inhibit the growth of P. gingivalis, P. intermedia, A. actinomycetemcomitans, and F. nucleatum (in vitro experiment) (Moman et al., 2020; Jansen et al., 2021)

  2. Inhibit the adhesion of A. actinomycetemcomitans, P. gingivalis, and P. intermedia (in vitro experiment) (Sliepen et al., 2008; Van Hoogmoed et al., 2008; Sliepen et al., 2009)
Streptococcus dentisani Increase the secretion of IL-10 and decline the level of IFN-γ induced by F. nucleatum in HGF-1 (in vitro experiment) (Esteban-Fernandez et al., 2019)

  1. Change cell wall structure of P. intermedia and induce cell lysis of F. nucleatum (in vitro experiment) (López-López et al., 2017)

  2. Suppress F. nucleatum and P. gingivalis growth and attachment to HGF-1 (in vitro experiment) (López-López et al., 2017)
Streptococcus cristatus Reduce the F. nucleatum-induced pro-inflammatory IL-8 production in oral epithelial cells (in vitro experiment) (Zhang et al., 2008)

  1. Produce arginine deiminase ArcA to inhibit fimbrial gene (fimA) expression and biofilm formation of P. gingivalis (in vitro experiment) (Xie et al., 2000; Xie et al., 2007)

  2. Inhibit adhesion and colonization of A. actinomycetemcomitans (in vitro experiment) (Sliepen et al., 2008)
Streptococcus gordonii, Streptococcus sanguinis, Streptococcus mitis –

  1. Reduce fimbrial gene (mfa1) expression of P. gingivalis (in vitro experiment) (Xie et al., 2000; Xie et al., 2007)

  2. Inhibit adhesion and colonization of A. actinomycetemcomitans, P. gingivalis, and P. intermedia on hard surfaces or epithelial cells (in vitro experiment) (Teughels et al., 2007; Sliepen et al., 2008; Van Hoogmoed et al., 2008)
Weissella Weissella cibaria

  1. Reduce the F. nucleatum-induced pro-inflammatory cytokine (IL-6 and IL-8) production in KB cells (in vitro experiment) (Kang et al., 2011)

  2. Inhibit NF-κB activation and NO production in response to periodontopathogen stimulation in macrophages (in vitro experiment) (Kim et al., 2020b)

  3. Reduce both the production of pro-inflammatory (TNF-α, IL-1β, IL-6) and anti-inflammatory (IL-10) cytokines (animal experiment) (Kim et al., 2020a)

  1. Co-aggregate with F. nucleatum, T. denticola, and P. gingivalis and inhibit the growth of F. nucleatum and P. gingivalis (in vitro experiment) (Kang et al., 2006b; Jang et al., 2016)

  2. Interfere with the adhesion of F. nucleatum (in vitro experiment) (Kang et al., 2011)

  3. Produce acid, H2O2, and N-acetylmuramidase to inhibit F. nucleatum, P. gingivalis, and P. intermedia (in vitro experiment) (Lim et al., 2018)

  4. Reduce the amount of plaque and F. nucleatum, P. gingivalis, P. intermedia, and T. forsythia levels in the oral cavity and P. gingivalis level in gingival tissues (animal experiment) (Do et al., 2019; Kim et al., 2020a)

  5. Reduce F. nucleatum in GCF (clinical trial) (Kang et al., 2020).
Recombinant probiotics Recombinant Lactobacillus paracasei – Express single-chain antibody fragments against RgpA gingipain to co-aggregate with P. gingivalis and kill it (in vitro experiment) (Marcotte et al., 2006)
Recombinant L. acidophilus Express FomA to induce the production of antibodies against FomA protein and prevent the infection of F. nucleatum and its co-aggregated P. gingivalis (in vitro experiment) (Ma et al., 2013) Present similar antibacterial activity and antibiotic sensitivity to the wild L. acidophilus, and its adhesive ability was improved (in vitro experiment) (Ma et al., 2018)

GCF, gingival crevicular fluid; OPG, osteoprotegerin.