Sex-specific differences in the occurrence of Fusobacterium nucleatum subspecies and Fusobacterium periodonticum in the oral cavity

The periodontitis-associated species Fusobacterium nucleatum (FN) has been implicated in several extra-oral diseases, including preterm birth and colorectal cancer. Due to its genetic and phenotypic heterogeneity, FN is classified in four subspecies which may differ in their disease potential. Here we compared the prevalence of FN subspecies and the close relative F. periodonticum (FP) via 16S rRNA gene analysis in saliva from 100 healthy individuals (60 females, and 40 males) from eleven countries spanning five continents. By focusing on the most abundant sequence types (i.e. analysis of approximately ten clone sequences each) the average number of FN/FP subspecies per individual differed significantly between females and males, i.e. 2.93 versus 2.5, respectively (P = 0.043). FN subsp. fusiforme/vincentii was significantly more prevalent in females vs males, with 2.85 vs. 1.68 sequence reads per individual, respectively (P = 0.012). A significant age-related difference was observed in females but not in males, i.e. 2.6 subspecies on average in females ≤ 30 years vs. 3.2 in females > 30 (P = 0.0076). Given the link between FN and systemic disorders our findings highlight the need for microbial studies at the subspecies level to further characterize the role of periodontal pathogens in diseases that affect females and males differently, e.g. colorectal cancer.