Probiotics Applications in Periodontitis Treatment

Periodontitis is a prevalent condition that can affect up to 90% of the global population. The risk of periodontitis might be associated with gum inflammation (bleeding) due to plaque accumulation [1, 2]. Overreacting immune responses in the teeth could lead to tissue destruction or the release of tissue-damaging protein-degrading enzymes. Hundreds or even thousands of microbial antigens provoke an immune response, usually serving protective functions. However, if prolonged, it can lead to risks such as soft and hard tissue breakdown. Periodontal inflammation results in the loss of supporting bone and tissue, causing tooth mobility, occasional pain and discomfort, reduced chewing function, and, ultimately, tooth loss in adults [3, 4]. Moreover, genetic and environmental factors, particularly smoking, genetic disorders, dermatology, hematology, immune suppression, and cancer, might also manifest in periodontitis. Adverse pregnancy outcomes, cardiovascular disease, stroke, respiratory disease, and diabetes may also be linked to common forms of periodontal disease.

Treatment and Prevention of Periodontitis

Prevention and treatment aim to control bacterial biofilm and other risk factors, halt disease progression, and restore lost tooth support  [5]. However, periodontitis often refers to common inflammatory disorders of gum and periodontal inflammation caused by disease-causing oral microbiota. Gingivitis, the mildest form of periodontitis, is widespread and easily addressed through simple and effective oral hygiene practices. Gingivitis affects 50–90% of adults worldwide. Deeper inflammation in tissues causing loss of supporting tissues and bone is referred to as periodontitis (Figure 1) [2]. Studies have proven that non-surgical periodontal treatment reduces periodontal inflammation and decreases inflammatory markers in the blood and reactive proteins. In some cases, doctors treat periodontitis by surgically removing the diseased arterial endothelium and clearing blocked arteries. Prevention comes in various forms, such as limiting smoking, minimizing diabetes, enhancing regular dental check-ups, and frequent dental cleanings [5].

Figure 1: Healthy teeth and teeth affected by periodontitis: a – Healthy tooth tissues; b – Gum inflammation; c – Clinical manifestation of periodontitis with tissue loss.

Mechanism of Probiotics in Improving Periodontitis

Health-promoting microorganisms derive probiotics (beneficial bacteria) when supplied in sufficient quantities [6, 7]. Studies have highlighted successful applications in various medical fields with eight known types of probiotics.

• Probiotics Combat Periodontitis-Causing Bacteria

Several strains of lactobacilli and streptococci isolated from healthy oral cavities exhibit antibacterial activity against Porphyromonas gingivalis, Prevotella intermedia, Aggregatibacter actinomycetemcomitans, và Fusobacterium nucleatum [8, 9]. Lactobacillus strains, including Lactobacillus paracasei và Lactobacillus acidophilus inhibit Staphylococcus aureus growth, a pathogen found in periodontitis, and suppress gas-forming Streptococci such as P. gingivalis and P. intermedia by producing lactic acid and other organic acids [10]. The growth of P. gingivalis is also inhibited by the hydrogen peroxide production of some beneficial bacterial strains isolated from commercial yogurt products. Plantaricin demonstrates antibacterial activity by inhibiting the growth of P. gingivalis. Nisin has significant antibacterial and antibiotic effects against gram-negative periodontal pathogens, including P. gingivalis, P. intermedia, A. actinomycetemcomitans, F. nucleatum, and Treponema denticola [11].

The antibacterial activity of probiotics is also linked to altering the host bacterial signaling and subsequent immune response. Some studies found that lactobacilli modulate the inflammatory response to periodontal pathogens. Specifically, when gum epithelial cells are infected with P. gingivalis, different immune responses of the host were noted after treatment with Lactobacillus and Bifidobacterium. While levels of inflammatory cytokines like interleukin (IL)-1β, IL-6 increase in the presence of P. gingivalis, their levels decrease after lactobacilli treatment [12]. Additionally, lactobacilli may activate a gene encoding IL-8, increasing its expression and counteracting its degradation by P. gingivalis, thus promoting an anti-inflammatory response against this pathogen.

• Some Preclinical and Clinical Studies on Probiotics Improving Periodontitis

Most preclinical studies have assessed the antibacterial effects of lactobacilli, bifidobacteria, and streptococci [13]. Other beneficial bacterial strains tested include the yeast Saccharomyces cerevisiae. Most studies evaluate changes in alveolar bone after probiotic treatment. Some studies showed that probiotic treatment often prevents alveolar bone loss [14, 15]. Reduced alveolar bone loss was observed in periodontal sites treated with Bacillus subtilis bacteria compared to untreated sites. Specifically, supplementing with probiotics containing B. subtilis reduced bone loss and protected the juvenile gut from inflammatory-induced changes due to periodontitis. Lactobacilli also significantly inhibits bone loss caused by periodontitis. Studies examining the impact of biological products in reducing alveolar bone loss and attachment loss or improving other clinical parameters suggest that the mechanisms involve both local and systemic effects, including local and systemic immune response modulation, antibacterial effects through different mechanisms, and stimulating bone formation. 

Another key goal of using probiotics in periodontitis treatment is to promote the growth of commensal or beneficial bacteria, including species like lactobacilli and streptococci, which exert anti-inflammatory effects and promote the host’s beneficial responses [16, 17]. In humans, these beneficial commensal bacteria have mostly been identified; however, similarities and differences within the human oral cavity remain unclear. Furthermore, the long-term changes in oral bacterial composition mediated by probiotics are still under-researched.

In conclusion, biological products tested using preclinical models show promising applications for treating periodontitis. In vitro models reveal that probiotics exhibit beneficial antibacterial and antibiotic effects, often mediated by bacteriocin production, enhanced growth under specific conditions, prioritizing their growth over pathogenic bacteria, enhanced adhesion and invasion, and beneficial adjustments to the host’s immune responses. In periodontitis treatment, probiotics may also improve preclinical outcomes (alveolar bone loss and attachment loss), microbiota, and immunity. However, the impact of probiotics on long-term changes in microbial composition requires further investigation.

References:

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