In a recent article published in Nature Communications, researchers performed a genomic investigation of oral resistome development, i.e., of genes that confer antimicrobial resistance (AMR).

Study: Development of the oral resistome throughout the first decade of life. Image Credit: Sergii Kuchugurnyi/Shutterstock

Background

Since AMR is a growing health and economic issue, characterizing the AMR of the human oral microbiome is of utmost importance. After the gut, the oral cavity houses essentially the most microbes throughout the human body.

Accordingly, researchers have identified antimicrobial resistance genes (ARGs) within the oral microbiome of neonates to adults. Furthermore, the oral microbiome is a well-recognized site where horizontal gene transfer (HGT) occurs, which, in turn, facilitates the event of antimicrobial-resistant infections.

In childhood, eating regimen, the introduction of solid foods, and the emergence of teeth change the composition of the oral microbiome. Host genetics also comes into play and influences ARG-carrying oral bacteria during childhood. Nevertheless, it has remained unexplored how commensal and pathogenic bacteria within the oral microbiome acquire and develop AMR during childhood.

One Health recognizes the connectedness of human and animal health as they share the identical environment. Because the oral microbiome is a major antimicrobial resistance (AMR) reservoir, its surveillance, as a part of the One Health Approach, is mandatory to combat AMR spread as a result of antibiotic overuse.

Concerning the study

Oral microbiome diversity increases as children get older. So, in the current study, researchers sequentially examined 530 oral metagenomes from 221 Australian twins and demonstrated the widespread presence of ARGs of their oral microbiome. They examined the event of the oral resistome, including taxonomic and functional association, along with the mobilization potential of ARGs.

As well as, they showed the way it significantly modified in composition with other microbiome constituents over the primary decade of life and in response to changes in oral health, e.g., dental caries and placement of restorations.

The dual study design allowed easy comparison of various AMR phenotypes of monozygotic (MZ) and dizygotic (DZ) twins. More importantly, it helped the researchers take a sneak peek into how genetics and environment influence the event of the oral resistome in children aged between 2.4 months and 10.8 years.

Results

Of the 221 twins, 124 and 97 were females and males children, respectively. The study results showed that the oral resistome of those children played a major role in AMR imbalance and transmission. It was also inherently dynamic.

Although scientists have observed that oral resistome accounts for lower than 1% of the known microbiome, on this study, they observed that AMR-related mobile genetic elements (MGEs) were extensively prevalent, as an illustration, the Tn916 transposase family. One other remarkable finding was that the mobilization potential of ARGs increased with the age of youngsters. Furthermore, genetics and environment, e.g., early feeding practices, influenced the oral resistome composition, identical to they influenced the oral microbiome. Moreover, oral health altered the resistome composition.

The longitudinal profiling of the oral metagenome also showed that the oral resistome was stable and returned to equilibrium after short-term perturbations. Its resilience remained unaffected by significant disturbances within the oral cavity throughout the first two and a half years of life as a result of tooth eruption and dietary changes. Nevertheless, oral resistome exhibited temporary changes in diversity before permanently stabilizing on the age of 5 years (T3). Quite the opposite, gut resistome substantially increases its ARG richness only throughout the first 12 months of life.

Functional investigations revealed that after T3, ARGs interacted with functional pathways, e.g., the mycothiol biosynthesis pathway, to facilitate the event of AMR. Mycothiol detoxifies antibiotics, enabling good bacteria to endure antibiotic exposure and eventually develop resistance. Individuals with higher ARG diversity also showed the next potential for biofilm constructing, e.g., sugar degradation pathways. In the long run, transcriptomics-based studies could explain the association between AMR and bacterial metabolism.

Taxonomic investigations of the oral resistome revealed the spread of AMR via HGT co-location of ARGs and insertion sequences (IS) in 27 species across various time points. They observed that oral commensals, corresponding to Streptococcus mitis and S. anginosus carried IS-associated ARGs. These species were exceptionally proof against treatment and passed resistance to latest environments they entered. These species exhibited an association with the Tn916 family of transposases and facilitated the co-carriage of two resistance genes, tetracycline resistance gene tet(m) and macrolide resistance gene erm(B).

The authors could determine the pattern of heritability reliably for T2 and T3 only, not T1. The heritability effect declined between T2 and T3. In contrast, the influence of normal and unique environmental effects increased on the oral resistome, likely because in comparison with infants, school-goers experience diverse environments, e.g., eating regimen and antibiotics. Moreover, the researchers noted that though indirect exposures, e.g., antibiotic use in food production, influenced oral resistome composition, protein consumption didn’t significantly affect resistome diversity.

Conclusions

To conclude, the study highlighted the importance of understanding how the oral resistome and its interactions with commensals and other bacterial species, restorative materials, etc., is critical to improving oral health. Because the connections between the oral cavity and respiratory, vascular, and digestive systems are intimate, mobilization of the oral resistome might need a long-term impact on systemic health beyond childhood.