Metagenome and Metabolic Pathways in Plaque Biofilms of Thai ELANE-Associated Neutropenic Patients: An Original Study and Scoping Review.

Objective: Congenital neutropenia, particularly ELANE-associated forms, is associated with recurrent oral infections and aggressive periodontitis. While ELANE deficiency compromises oral health, its relationship to plaque biofilm ecology and metabolic function remains unclear. The oral microbiome-metabolome interplay in this condition remains largely uncharacterized globally. Here, we address this gap by characterizing the dental plaque metagenome and inferred metabolic pathways in a defined cohort of Thai neutropenia patients. Materials and Methods: In this exploratory study, we sequenced dental plaque samples from a defined cohort of nine individuals: three patients with severe congenital neutropenia or cyclic neutropenia (CyN) with confirmed ELANE variants, and six from age- and gender-matched healthy controls. Shotgun metagenomics was used for genomic analysis, followed by comprehensive microbiota examination. Subsequently, MetaCyc, a curated database, was used for in silico analysis and comparisons of the predicted functional pathways between the test and control plaque biofilms. Results: The principal coordinate analysis plot and heat map revealed distinct segregation of microbial profiles between the patients and control groups. A significant variation in the proportions of the five core phyla was noted in patients and controls. Two commensal species, Aggregatibacter sp oral taxon 458 and Leptotrichia sp oral taxon 212, were enriched in the controls. Conversely, four species were significantly enriched in the patients, Selenomonas flueggei, Streptococcus milleri, Kingella oralis, and Actinobaculum sp oral taxon 183; the latter being notably elevated across all patients. The MetaCyc in silico analyses suggested predicted enrichment of functional pathways associated with inflammation and oxidative stress in patients, including L-methionine biosynthesis IV, formaldehyde assimilation III, L-rhamnose degradation, and the superpathway of (R,R)-butanediol biosynthesis pathways. Conclusion: Our study advances the understanding of ELANE-associated periodontitis by moving beyond descriptive microbiota analysis to suggest potential associations between host immune deficiency, microbial dysbiosis, and the microbiota-associated metabolic pathway alterations. These findings provide preliminary insights into targeted periodontal care in neutropenic patients, though further validation in larger cohorts is required.