Fusobacterium nucleatum is a gram-negative anaerobe ubiquitous to the oral cavity. It is associated with periodontal disease. It is also associated with preterm birth and has been isolated from the amniotic fluid, placenta, and chorioamnionic membranes of women delivering prematurely. Periodontal disease is a newly recognized risk factor for preterm birth. This study examined the possible mechanism underlying the link between these two diseases. F. nucleatum strains isolated from amniotic fluids and placentas along with those isolated from orally related sources invaded both epithelial and endothelial cells. The invasive ability may enable F. nucleatum to colonize and infect the pregnant uterus. Transient bacteremia caused by periodontal infection may facilitate bacterial transmission from the oral cavity to the uterus. To test this hypothesis, we intravenously injected F. nucleatum into pregnant CF-1 mice. The injection resulted in premature delivery, stillbirths, and nonsustained live births. The bacterial infection was restricted inside the uterus, without spreading systemically. F. nucleatum was first detected in the blood vessels in murine placentas. Invasion of the endothelial cells lining the blood vessels was observed. The bacteria then crossed the endothelium, proliferated in surrounding tissues, and finally spread to the amniotic fluid.
Opportunistic pathogenic microbes are indigenous to the female lower genital tract and etiologic in many types of pelvic infections and, apparently, a portion of preterm birth (PTB) cases. Bacterial vaginosis (BV) is a clinical syndrome based on an altered genital microflora in which Gardnerella vaginalis; anaerobic species primarily among Prevotella, Porphyromonas, Bacteroides, Peptostreptococcus, and Mobiluncus; Mycoplasma hominis; and Ureaplasma urealyticum become predominant in vaginal secretions. This BV complex of microbes, compared to a normal vaginal microflora dominated by facultative lactobacilli, is associated with significantly increased risks for preterm labor, preterm premature rupture of membranes, PTB, and other perinatal infectious complications. Pathogenetic mechanisms include an ascending route of infection and/or inflammatory process due to microbial products and maternal and/or fetal response(s) with production of prostaglandins and cytokines. In the presence of periodontal disease, oral opportunistic pathogens and/or their inflammatory products also may have a role in prematurity via a hematogenous route. Fusobacterium nucleatum, a common oral species, is the most frequently isolated species from amniotic fluid cultures among women with preterm labor and intact membranes. Also, the species and subspecies of fusobacteria identified from amniotic fluid most closely match those reported from healthy and diseased subgingival sites, namely F. nucleatum subspecies vincentii and F. nucleatum subspecies nucleatum, compared to strains identified from the lower genital tract. Although these fusobacteria also could be acquired through cunnilingus from a partner, new data associating maternal periodontal disease with preterm low birth weight taken with the isolation of F. nucleatum, Capnocytophaga, and other oral species from amniotic fluid support further study of a possible additional route, oral-hematogenous, to PTB.
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