The Efficacy Of Probiotics And Lactoferrin In The Treatment Of Black Stain: A Systematic Review Of The Literature

Abstract

Introduction: In daily dental practice, dental hygienists and the dental team frequently manage patients with black stain, a common extrinsic pigmentation of chromogenic origin affecting tooth surfaces. Recent interest has focused on the role of lactoferrin and probiotics as preventive and therapeutic strategies for this condition.
Objective: This systematic review aimed to evaluate the efficacy of lactoferrin and probiotics in the prevention and treatment of black stain by critically analyzing the available scientific evidence.
Methods: A systematic literature review was conducted using PubMed/MEDLINE, Embase, and Cochrane databases. The review followed the PRISMA 2020 guidelines. After applying predefined inclusion and exclusion criteria, four studies were selected for qualitative analysis.
Results: The available evidence suggests that both lactoferrin and probiotics may contribute to reducing the formation of black stains. Lactoferrin appears to limit pigmentation by binding iron ions involved in stain formation, whereas probiotics help restore the balance of the oral microbiota, reducing the proliferation of chromogenic bacteria. The findings indicate that the combined use of lactoferrin and probiotics may represent a promising approach for managing black stain, although the current evidence remains limited.
Conclusions: Existing evidence on the effectiveness of lactoferrin and probiotics for the prevention and treatment of black stain is scarce and based on a small number of studies. While preliminary findings are encouraging, further well-designed clinical studies are needed to confirm their efficacy and to determine whether the combined use of lactoferrin and probiotics can be recommended as an effective therapeutic strategy for the management of black stain.

INTRODUCTION

Black stain represents a frequent aesthetic and clinical problem in pediatric and adolescent dentistry. These dental stains, often associated with the presence of chromogenic bacteria, accumulate on the tooth surface, causing dyschromia that can negatively influence patients' self-esteem and motivation towards proper oral hygiene. (1, 2)

In recent years, interest in alternative therapeutic approaches has led to the exploration of the use of lactoferrin and probiotics in combined treatments. Lactoferrin is a glycoprotein present in milk and other biological fluids, known for its antimicrobial and anti-inflammatory properties. It acts by sequestering iron ions, which are fundamental for the growth of microorganisms, including those responsible for black stain, thus reducing bacterial colonization and promoting a favorable balance of the oral microbiota. (3)

Fig. 1. The image shows an example of black stain affecting the anterior dental arches (Partynia, CC BY-SA 4.0, via Wikimedia Commons).

Probiotics, on the other hand, are live microorganisms that provide health benefits to the host by modulating the microbiota. Strains such as Streptococcus salivarius M18 and Lactobacillus reuteri have demonstrated potential in reducing bacterial plaque and preventing periodontal diseases. However, despite their promising properties, the literature is lacking regarding the combined use of lactoferrin and probiotics in the treatment of black stain. (4)

The objective of this study is to examine the available evidence on the efficacy of lactoferrin and probiotics, both as single and potentially combined therapies, for the treatment of black stain.

MATERIALS AND METHODS

A systematic review of the literature was conducted using the PubMed/MEDLINE, Embase, and Cochrane databases, following the PRISMA method (5). The search was completed on October 18, 2024, and included the search strings in table 1.

Tab. 1.  

The search strings were developed using the PICO protocol.

The inclusion criteria comprised are shown in table 2. While the exclusion criteria were are shown in table 3.

Tab. 2.  

Tab. 3.  

RESULTS

A total of 100 articles were found, 42 for the first search string and 54 for the second string. The third query yielded no results on any database searched. After eliminating duplicates, 42 articles for lactoferrin and 48 for probiotics were analyzed. Of these, four studies were selected for the review after applying the inclusion and exclusion criteria (table 4 and 5).

Tab. 4. PRISMA Flow Diagram of the First Search String

Tab. 5. PRISMA Table for the Second Search String

The tables 6 and 7 report the articles that were included in the review.

Tab. 6.  

Tab. 7.  

Lactoferrin

The study by Sangermano R. et al. (6) is observational in nature and involved subjects affected by black stain. The protocol involved the oral administration of two tablets of Lactoferrin (Lf) (containing 50 mg of Lf and 50 mg of D-Biotin) twice a day, after thorough oral hygiene. The results obtained demonstrate that Lf represents an effective and innovative treatment for counteracting black stain, as it is able to sequester the excess iron ions present in saliva.

The study by Rosa L. et al. (7) describes the complexity of the oral microbiota and evaluates the efficacy of lactoferrin through an observational study, in which Lf tablets were administered twice a day for a period of 90 days. The data collected highlight that the availability of iron in saliva is a determining factor for the formation of black stain. In particular, lactoferrin is able to chelate two ferric ions per molecule and establish bonds with anionic surfaces, demonstrating antioxidant, bacteriostatic, bactericidal, anti-biofilm, anti-adhesive, anti-invasive, and anti-inflammatory properties.

Probiotics

The article by Gobbi E. et al. (8) analyzes the inhibitory effect of two commercial probiotics, Streptococcus salivarius M18 and Lactobacillus reuteri Prodentis, against the microorganisms associated with black stain. The results indicate that both probiotics are able to reduce the presence of pathogens related to black stain, in particular Aggregatibacter actinomycetemcomitans and Actinomyces naeslundii, in a dose-dependent manner. In detail, Streptococcus salivarius M18 showed superior antimicrobial activity compared to Lactobacillus reuteri Prodentis. Furthermore, Actinomyces naeslundii is less susceptible to the action of probiotics compared to Aggregatibacter actinomycetemcomitans. These results highlight the ability of probiotics to inhibit the growth of microorganisms associated with black stain, suggesting that such strains could be evaluated for therapeutic use in the treatment of this condition.

In the randomized study by Bardellini E. et al. (9), the efficacy of the oral probiotic Streptococcus salivarius M18 is evaluated in children affected by black stain. 58 children aged between 4 and 10 years were involved, randomly divided into two groups: group A received the product containing Streptococcus salivarius M18 once a day for 3 months, while group B received no treatment. The evaluation of black stain was performed after 3 and 6 months. The results show that, after 3 months, black stain was present in 6 of the 28 children in group A and in 13 of the 26 children in group B. After 6 months, black stain was found in 9 of the 28 children in group A and in 14 of the 26 children in group B. Therefore, the administration of Streptococcus salivarius M18 via oral tablets seems to contribute to slowing the growth of black stain in children.

DISCUSSION

The results confirm that both lactoferrin and probiotics have significant potential in the treatment of black stain, but independently. Lactoferrin acts primarily by sequestering iron, a key element for the growth of chromogenic bacteria, while probiotics modulate the oral microbiota, favoring an environment less prone to the formation of black stains.

However, the combination of these two therapies remains unexplored. The association of lactoferrin and probiotics could theoretically offer a synergistic effect, combining iron sequestration with the promotion of beneficial bacteria. This hypothesis, if confirmed, could lead to more effective therapeutic protocols. Controlled clinical trials are needed to evaluate the safety, efficacy, and optimal doses of this combination.

Fig. 2. The image below illustrates an example of black stain on the posterior teeth.

A further aspect to consider is the need to evaluate the efficacy of home treatments compared to professional ones, in particular to improve patient adherence and long-term results.

CONCLUSIONS

The review highlights that lactoferrin and probiotics represent promising approaches for the management of black stain. However, the absence of studies on the combined use of these agents represents a significant gap in the literature.

The combination of lactoferrin and probiotics could potentially revolutionize the treatment of black stain, but further research is needed to evaluate its efficacy and define standardized protocols. Investing in future studies on this topic is essential to improve the quality of care and optimize the management of this widespread dental condition.

Other information

Corresponding authors: Simone Sevi | email: simone.sevi@gmail.com