Fusobacterium nucleatum is a gram-negative anaerobe ubiquitous in the oral cavity. It is associated with periodontal disease, premature birth and has been isolated from amniotic fluid, placenta and chorioamniotic membranes of women who give birth prematurely. Periodontal disease is a recently recognized risk factor for preterm birth. Invasive capacity can enable F. nucleatum to colonize and infect the pregnant uterus. Transient bacteremia caused by periodontal infection may facilitate the transmission of bacteria from the oral cavity to the uterus.

To test this hypothesis, F. nucleatum was injected intravenously into pregnant mice.

The injection has resulted in preterm birth, stillbirths, and intermittent live births. The bacterial infection was confined to the interior of the uterus, without spreading systemically, and F. Nucleatum was first detected in the blood vessels of mouse placentas [invasion of the endothelial cells that line the blood vessels].

The bacteria then crossed the endothelium, multiplied

into the surrounding tissues and eventually spread into the amniotic fluid. The pattern of infection parallels that in humans. This study represents the first evidence that F. nucleatum can be hematogenously transmitted to the placenta and cause adverse pregnancy outcomes. The results strengthen the link between periodontal disease and preterm birth. Periodontal disease is a highly prevalent infectious disease and is caused by colonization with various gram-negative, anaerobic bacteria in plaque. Preterm birth is the number one cause of infant mortality and morbidity [7 to 11% of all births in the US alone]. These two seemingly unrelated health problems have recently been linked, with periodontal disease being recognized as a potential risk factor for preterm birth. Epidemiological studies have shown that intrauterine infections are particularly prevalent among women who give birth prematurely.

There are four possible mechanisms for germs to spread in the uterus, an otherwise sterile environment: (i) organisms from the vagina and cervix ascend into the uterus. (ii) the organisms originate elsewhere and are bloodborne; (iii) organisms from the peritoneal cavity through the fallopian tube. (iv) are accidentally inoculated into the uterus during invasive procedures [amniocentesis and chorionic villus sampling].

Ascending infection is considered the most common route of infection.

Bloodborne spread of organisms from other parts of the body to the uterus is a second route.

A variety of organisms have been isolated from placenta, amniotic fluid, and chorioamnion cultures, with Ureaplasma urealyticum, Mycoplasma hominis, and Bacteroides urealyticus being the most common, which are INDIGENOUS opportunistic pathogens and are often associated with bacterial vaginosis, a risk factor for preterm labor.

SOURCE: ASM Journals Infection and Immunity 2004