Antimicrobial resistance genes in the oral microbiome

Antimicrobial resistance (AMR) represents a critical global health challenge, with the World Health Organisation identifying it as one of the top ten threats to humanity directly responsible for 1.27 million deaths in 2019¹. The oral cavity, with its diverse and densely populated microbiome, is increasingly recognised as a reservoir for ARGs^2,3,4. These genes can be transferred between bacterial species through horizontal gene transfer mechanisms such as conjugation, transformation, and transduction, potentially disseminating resistance to pathogenic bacteria both within and beyond the oral environment⁴.

The systematic review by Sukumar et al.⁵ provides a comprehensive analysis of the current state of knowledge regarding the oral resistome, the collection of all ARGs present in the oral microbiota. By focusing on studies employing molecular detection techniques such as PCR and NGS, the authors highlight the advancements in scientific ability to detect and characterise ARGs within the oral cavity.

The use of multiple databases and a broad time frame (from 2015 to 2023) ensured a wide capture of relevant studies. The inclusion criteria were well-defined, focusing on clinical studies that utilised molecular techniques to detect ARGs in human oral samples. The independent screening and assessment by multiple reviewers minimised selection bias and enhanced the reliability of the findings.

This systematic review demonstrates that NGS metagenomics identifies a higher number of ARGs and associated bacterial species compared to PCR. Specifically, NGS studies detected an average of 34 ARGs and 177 ARG-carrying species, whereas PCR studies identified an average of 7 ARGs and 25 species. This illustrates the superior sensitivity and comprehensiveness of NGS in characterising the oral resistome. The identification of ARGs across various regions of the oral cavity, with the supragingival biofilm and saliva showing the highest richness, provides valuable information on the distribution of resistance genes. The detection of ARGs conferring resistance to critical antibiotic classes, including tetracyclines and macrolides, across all sampled locations is particularly concerning given the clinical importance of these antibiotics.

The small number of included studies (n = 15) and the heterogeneity among them limit the generalisability of the findings. Variations were noted in study design, sample collection methods, participant demographics and analytical techniques. The predominance of PCR-based studies over NGS may reflect resource constraints, as NGS is more technologically demanding and costly. As NGS sequences all the DNA in a sample without a priori knowledge of the genes present, it inherently provides more comprehensive and unbiased insights into the resistome than PCR. NGS can detect a wider range of ARGs, including novel or unexpected genes, and can identify ARGs in a broader array of bacterial species. In contrast, PCR is restricted to a predefined set of ARGs and cannot detect genes outside of those targets.

There was no quality assessment of the included studies which limits the ability to fully appraise the validity and reliability of the findings. Moreover, the absence of a meta-analysis due to heterogeneity prevents drawing any definitive conclusions from pooled data.

The detection of ARGs in streptococcal species associated with infective endocarditis emphasises the importance of investigating oral bacteria that can cause systemic infections. Additionally, the identification of ESKAPE pathogens in the oral cavity is alarming, given their role in hospital-acquired infections and their multidrug-resistant nature.

Future research should prioritise the use of NGS metagenomics (over PCR) to provide a more comprehensive understanding of the oral resistome. Longitudinal studies examining the impact of factors such as antibiotic exposure, oral hygiene practices and systemic health conditions on the dynamics of ARGs in the oral microbiome are essential.