Antimicrobial resistance genes in the oral microbiome.

A Commentary On: Sukumar S, Rahmanyar Z, El Jurf H Q et al. Mapping the oral resistome: a systematic review. J Med Microbiol 2024; https://doi.org/10.1099/jmm.0.001866 .

Design: This systematic review, without meta-analysis, aimed to map the oral resistome by analysing clinical studies that detected bacterial antimicrobial resistance genes (ARGs) in the oral cavity using molecular techniques.

Data Sources: The researchers used Medline, Embase, Web of Science, CINAHL and Scopus databases from January 2015 to August 2023.

Study Selection: This systematic review included cross-sectional or longitudinal clinical studies that detected ARGs using molecular techniques; specifically polymerase chain reaction (PCR) or next-generation sequencing (NGS) metagenomics for samples from the oral cavity (saliva, gingival biofilm, pulp, or oral mucosa). Studies were excluded if they were in vitro or animal studies, literature reviews and not focused on ARG detection.

Data Extraction And Synthesis: Five reviewers independently screened titles and abstracts based on inclusion criteria. Full-text reports were then independently assessed for eligibility by three reviewers. Extracted data encompassed publication details, sample size, country, molecular methods used, number of ARGs detected, participants' health status, antibiotic exposure, and sample location within the oral cavity.

Results: Out of 580 initially identified studies, 15 met the inclusion criteria. These studies, published between 2015 and 2023 from 12 different countries, employed either PCR (n = 10) or NGS metagenomics (n = 5) to detect ARGs from a pool of 1486 participants (1 study did not report on the number of participants). PCR-based studies identified an average of 7 ARGs (range 1-20), while NGS studies identified an average of 34 ARGs (range 7-70). In total, 159 unique ARGs conferring resistance to 22 antibiotic classes were identified across six regions of the oral cavity. The supragingival biofilm and saliva exhibited the highest richness of ARGs, defined by the number of unique ARGs detected. Genes conferring resistance to 19 antibiotic classes were present in the supragingival biofilm. Notably, 49 ARGs, including tetracycline and macrolide resistance genes, were found across all sampled locations, indicating a widespread distribution within the oral cavity. Thirteen studies reported on bacterial species associated with ARGs. NGS studies identified a mean of 65 ARG-carrying bacterial species, compared to a mean of 4 species in PCR studies. Specifically, 25 ARG-carrying species were identified in PCR studies, while NGS studies identified 177 species. Four studies reported ARGs associated with streptococcal species implicated in distant-site infections such as infective endocarditis. ESKAPE pathogens (group of highly virulent multidrug-resistant bacteria) were detected with ARGs in various oral sites using both PCR and NGS methods. Comparisons between healthy and diseased states revealed that a healthy oral microbiome harbours a more diverse resistome at the antibiotic class level. The supragingival resistome demonstrated the richest composition in both health and disease, with tetracycline ARGs predominating in the supragingival and saliva resistomes in cases of dental caries.

Conclusions: The analysis of the oral resistome from these 15 studies identified three ARGs present in all sites of the oral cavity, suggesting the presence of a core resistome. NGS studies provided greater insights compared to PCR studies; however, the overall research base is limited. Further comprehensive studies are necessary to fully map the oral resistome.