Oral-predominant microbial and functional dysbiosis in craniofacial microsomia: species-level profiling with compartment-matched statistical testing

Background Craniofacial microsomia (CFM) is the second most common congenital craniofacial anomaly. Oral dysbiosis has been described at genus level, but whether it extends beyond the mouth, or relates to the defining alveolar bone deficiency, is unknown.Patients/materials and methods Oral and gut microbiomes of 45 children with CFM and 18 matched controls were profiled at species level by 2bRAD-M, alongside shotgun metagenomes and blood, faecal and oral metabolomes. Alveolar bone loss was quantified on computed tomography against each patient's contralateral side. Centred-log-ratio methods with Benjamini-Hochberg false-discovery-rate (FDR) control were used throughout. Compartment specificity was tested formally by a group-by-compartment interaction model in the 58 participants with paired oral and gut profiles, by sample-size-matched subsampling, and by minimum-detectable-effect calculation.Results Oral alpha diversity was higher in CFM than in controls (Shannon P = 0.014; all three alpha-diversity indices P < 0.05). Four species-level taxa were depleted after false-discovery-rate (FDR) correction (q < 0.05), and 21 interpretable metagenomic pathways differed between groups among 38 FDR-significant pathways. These annotations were enriched for carbohydrate transport, glycan processing and cell-surface or biofilm-related functions, but they are not specific markers of a cariogenic or pathogenic community. No FDR-robust gut or systemic signature was detected. At the species level, the oral and gut analyses were power-matched (minimum detectable |r| = 0.74 at the FDR-equivalent threshold), and the group-by-compartment interaction for Shannon diversity was significant (P = 0.026). This comparison supports an oral-predominant taxonomic pattern but does not establish biological absence of a gut effect. The functional comparison was not power-matched. In the patient-only post hoc analyses, the oral functional pattern was not associated with tooth-brushing frequency, sugary-drink intake or caries burden. Affected-side alveolar bone density was lower than contralateral density (paired P < 0.001) and was not associated with anatomical severity grade.Conclusions CFM was associated with an oral-predominant taxonomic and functional microbiome pattern. The matched-power comparison is informative for taxonomic analyses but does not exclude a biologically meaningful gut effect, and the functional comparison remains underpowered. These observations motivate prospective investigation of local, biofilm-directed interventions and of quantitative alveolar bone assessment as a follow-up endpoint.