Oropharyngeal microbiome signatures associated with meningococcal carriage in healthy young adults

Neisseria meningitidis (Nm) colonizes the oropharynx of healthy individuals, yet the relationship between the oropharyngeal microbiome and meningococcal carriage remains poorly characterized. We studied the oropharyngeal microbiome in relation to Nm carriage and capsular phenotype in a cohort of healthy young adults.

We enrolled 202 Nm carriers (of whom 101 harbored invasive capsular strains (B, C, W, X, Y)) and 202 matched non-carriers for microbiome analysis using 16S rRNA gene amplicon sequencing of oropharyngeal swabs. We compared the microbiome between carriers and non-carriers, carriers of invasive and non-invasive strains, and smokers and non-smokers, using alpha and beta diversity and differential abundance analyses. Isolate genomes were analyzed for the prp locus.

Carriers exhibited significantly higher Simpson diversity (p≤0.01) and distinct community composition (p=0.0002) compared to non-carriers. Differentially abundant taxa included Stomatobaculum, Lachnoanaerobaculum, Granulicatella, and Atopobium (enriched in carriers), and Epsilonbacteraeota and Patescibacteriota (enriched in non-carriers). Among carriers, invasive capsular strain carriers demonstrated significantly higher alpha diversity across all metrics and distinct beta diversity compared to non-capsular carriers. Notably, Campylobacter (Epsilonbacteraeota), Rothia, and Leptotrichia were enriched in capsular carriers, a pattern directionally opposite to that observed in the carrier vs. non-carrier comparison. Whole genome sequencing of Nm isolates revealed that the intact propionate utilization pathway (prp gene cluster) was far more prevalent in invasive capsular (62%) than in non-invasive isolates (10.5%, p<0.0001). Whether a metabolic relationship exists between the Campylobacter-enriched capsular carrier microbiome and propionate-utilizing Nm strains cannot be established from these genus-level data. Differences in composition between carriers and non-carriers remained after stratification by smoking status.

Nm carriage was associated with a distinct oropharyngeal microbiome, characterized by community reorganization rather than diversity loss, with divergent profiles between capsular and non-capsular carriers and a notable enrichment of Campylobacter alongside an intact prp locus in invasive capsular strains. Taken together, these findings identify microbial features that may shape meningococcal colonization and warrant longitudinal, species-level investigations to define their mechanistic and translational relevance.