In a recently published article in Nature Communicationsthe researchers carried out a genetic investigation of the development of oral resistance, that is, of genes that confer antimicrobial resistance (AMR).
As antimicrobial resistance is a growing health and economic issue, determining microbial resistance in the human oral microbiome is of paramount importance. After the gut, the oral cavity houses most of the microbes within the human body.
Accordingly, the researchers identified antimicrobial resistance genes (ARGs) in the oral microbiome of newborns to adults. Moreover, the oral microbiome is a well-known site where horizontal gene transfer (HGT) occurs, which in turn facilitates the development of antimicrobial-resistant infections.
In infancy, diet, the introduction of solid foods, and the appearance of teeth alter the composition of the oral microbiome. Host genes also play a role and influence ARG-carrying oral bacteria during childhood. However, how commensal and pathogenic bacteria in the oral microbiome acquire and develop antimicrobial resistance during childhood has remained unexplored.
One Health recognizes the interdependence between human and animal health because they share the same environment. Because the oral microbiome is an important reservoir of antimicrobial resistance (AMR), monitoring it, as part of the One Health approach, is essential to combat the spread of AMR due to antibiotic overuse.
The diversity of the oral microbiome increases as children get older. Therefore, in this study, the researchers examined 530 oral metagenomes by sequencing from 221 Australian twins and demonstrated the widespread presence of ARGs in the oral microbiome. They examined the evolution of the orogenic resistance, including taxonomic and functional association, as well as the mobilization potential of ARGs.
In addition, they showed how it changed dramatically in composition with other components of the microbiome over the first decade of life and in response to changes in oral health, for example, dental caries and placement of restorations.
The double-study design allowed easy comparison of the variable AMR phenotypes of monozygotic (MZ) and dizygotic (DZ) twins. More importantly, it helped the researchers peek into how genes and environment influence the development of oral resistance in children between the ages of 2.4 months and 10.8 years.
Of the 221 twins, 124 and 97 were female and male, respectively. The results of the study showed that the oral resistance of these children played an important role in the imbalance of antimicrobial resistance and transmission. She was also dynamic in nature.
Although the scientists noted that oral resistance represented less than 1% of the known microbiome, in this study, they noted that mobile genetic elements associated with antimicrobial resistance (MGEs) were widespread, for example, Tn916 transposase family. Another fascinating finding is that the mobilization potential of ARG increases with age in children. Moreover, genetic and environmental factors, such as early feeding practices, affected the composition of oral resistance, just as they did the oral microbiome. Moreover, oral health changed the resistant formulation.
Longitudinal profiling of the oral metagenome also showed that the oral metagenome was stable and returned to homeostasis after short-term perturbations. Its flexibility remained unaffected by significant disturbances in the oral cavity during the first two and a half years of life due to eruption of teeth and dietary changes. However, the orally resistant showed temporary changes in diversity before stabilizing permanently at the age of five years (T3). Conversely, gut resistance significantly increases ARG richness only during the first year of life.
Functional investigations revealed that after T3, ARGs interacted with functional pathways, for example, the mycothiol biosynthesis pathway, to facilitate the development of AMR. Mycothiol detoxifies antibiotics, enabling good bacteria to withstand antibiotic exposure and eventually develop resistance. Individuals with higher ARG diversity also showed higher biofilm building potential, for example, glycolytic degradation pathways. In the future, transcription-based studies could explain the relationship between antimicrobial resistance and bacterial metabolism.
Taxonomic investigations of the oro-resistant revealed the prevalence of antimicrobial resistance via the common HGT site of ARGs and insertion sequences (IS) in 27 species across different time points. Note that oral compensation, eg streptococcal infection; And S. anginosus carried ARGs associated with IS. These species were exceptionally resistant to treatment and to the new environments they were introduced to. These species exhibited association with Tn916 A family of transposases facilitating the co-transfer of two resistance genes, the tetracycline resistance gene tet (m) and the macrolide resistance gene (B).
The authors were able to reliably identify the inheritance pattern in T2 and T3, but not in T1. The effect of heredity decreased between T2 and T3. In contrast, the influence of standard and unique environmental influences on oral resistance increased, likely because compared to infants, schoolgoers are faced with diverse environments, such as diet and antibiotics. Furthermore, the researchers noted that although indirect exposure to, for example, antibiotic use in food production, affected the composition of oral resistance, protein consumption did not significantly affect the diversity of resistance.
In conclusion, the study highlights the importance of understanding how oral resistance, and its interactions with symbionts, other bacterial species, restorative materials, etc., is critical to improving oral health. Because the connections between the oral cavity and the respiratory, vascular, and digestive systems are intimate, oral resistive mobilization may have a long-term effect on systemic health beyond infancy.