OdontoTest: combined study

The microbial flora or oral microbiota is made up of a set of microorganisms that form a true microecosystem in the oral cavity. Its functions include protecting the host against infections caused by colonisation of the oral cavity by pathogenic microorganisms from the outside and from other cavities such as the ear and nose, as well as stimulating the immune system and keeping the mucous membranes in good condition.

The composition, abundance and diversity of microbial species in the oral flora depends on many factors.

• During the first years of life, the main route of transmission of micro-organisms in the oral cavity is from mother to child through direct contact and breastfeeding (vertical transmission).
• Subsequently, the route of transmission through direct contact with other family members, including the father, siblings and other potential caregivers (horizontal transmission), as well as other environmental factors, such as diet, oral hygiene, antibiotic intake and smoking, becomes important.

The variability is so great that no two people have completely identical oral microbial flora.

To date, the Human Oral Microbiome Project has identified more than 700 microbial species in the oral cavity, with the generaNeisseria, Spreptococcus, Actinomyces, Lactobacillus, Veillonella and Granulicatella being the most representative in quantitative terms.

Less than 1% of the species identified in the oral microbiota are involved in the development of caries and periodontitis. An imbalance in the normal microbial populations of the oral cavity may favour the overgrowth of this small group of aciduric and acidogenic microorganisms with pathogenic potential.

• The following microbial agents are involved in the pathogenesis of caries: Streptococcus mutans, Lactobacillus spp. and Actinomyces spp. Of these microorganisms Streptococcus mutans has the highest cariogenic potential.
• The pathogenesis of periodontitis is due to other micro-organisms classified into two complexes, according to the degree of pathogenicity.
  • The red complex includes three of the most pathogenic periodontal bacteria: Tannerella forsythia, Treponema denticola and Porphyromonas gingivalis.
  • The second group of periodontal pathogenic species is known as the orange complex and includes Prevotella intermedia, Fusobacterium nucleatum and Parvimonas micra.
• Another microorganism with great periodontopathogenic potential is Aggregatibacter actinomycetemcomitans, which acts as an immunosuppressive agent of the host periodontal defence system and alveolar bone homeostasis.

Based on the phenotype-SNPs association provided by the SNPedia database, the recommendations of the American Dental Association and the literature sources consulted, a total of five variants assessing individual susceptibility to the development of caries and periodontitis have been selected, prioritising those that have been previously identified by GWAS (genome-wide association studies) and subsequently validated by independent trials or meta-analysis studies. These variants are as follows:

• rs1047031 (GLT6D1) 
• rs1047031 (DEFB1)
• rs2046315 (MMP16)
• rs17878486 (AMELX)
• rs1143634 (IL1B)

These are mainly genes that play a role in the composition of the tooth and the inflammatory response of the host. The presence of any of these variants per se does not imply that the carrier will develop caries or periodontitis, as both conditions are the result of a multifactorial process with several factors involved.

The rs1047031 variant is located in GLT6D1, a gene with a high expression rate in gums. The exact function of this gene is currently unknown. However, the C allele of this gene variant has been associated with the development of severe periodontitis in different populations.

The rs1047031 variant is located in the regulatory region of the DEFB1 gene, which encodes a defensin family protein with broad-spectrum antimicrobial activity. The DEFB1 gene appears to play an important role in the maintenance of oral health. The T allele of rs1047031 has been associated with chronic and severe periodontitis, in addition to other oral cavity pathologies such as caries. The risk is higher when the homozygous recessive genotype for this allele (TT genotype) is present.

The rs2046315 variant is located in the regulatory region of the MMP16 gene. This gene encodes a protein of the metalloprotein family that participates in the degradation of extracellular proteins in multiple physiological processes and plays an important role in cariogenic processes. In fact, the T allele of this variant has been associated with an increased risk of caries development.

The rs17878486 variant is located in AMELX, a gene encoding a prostaglandin that plays a very important role in the development of tooth enamel. The T allele of this variant has been associated with an increased risk of caries, with the TT and TC genotypes being the most at risk. However, this allele has a high allele frequency in the European population (around 85%).

The rs1143634 variant is located in the IL1B gene, which belongs to the interleukin family, and is involved in several processes necessary to initiate and maintain the inflammatory response. Altered IL1Bla protein values have been found in patients carrying the T allele of this gene variant with periodontitis. This allele has been associated with chronic periodontitis, with carriers of this allele (TT and TC genotypes) having an increased risk of periodontitis.