Han Yiping W, Redline Raymond W, Li Mei, Yin Lihong, Hill Gale B, McCormick Thomas S
Department of Periodontics, School of Dental Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4905, USA.
Infect Immun. 2004 Apr;72(4):2272-9. doi: 10.1128/IAI.72.4.2272-2279.2004.
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. The pattern of infection paralleled that in humans. This study represents the first evidence that F. nucleatum may be transmitted hematogenously to the placenta and cause adverse pregnancy outcomes. The results strengthen the link between periodontal disease and preterm birth. Our study also indicates that invasion may be an important virulence mechanism for F. nucleatum to infect the placenta.
具核梭杆菌是一种革兰氏阴性厌氧菌，广泛存在于口腔中。它与牙周病有关。它还与早产有关，并且已从早产妇女的羊水、胎盘和绒毛羊膜中分离出来。牙周病是一种新发现的早产风险因素。本研究探讨了这两种疾病之间联系的潜在机制。从羊水和胎盘中分离出的具核梭杆菌菌株以及从口腔相关来源分离出的菌株均可侵袭上皮细胞和内皮细胞。这种侵袭能力可能使具核梭杆菌在妊娠子宫中定殖并感染。牙周感染引起的短暂菌血症可能促进细菌从口腔传播至子宫。为验证这一假设，我们给怀孕的CF-1小鼠静脉注射具核梭杆菌。注射导致早产、死产和非持续性活产。细菌感染局限于子宫内，未发生全身扩散。具核梭杆菌首先在小鼠胎盘的血管中被检测到。观察到血管内皮细胞被侵袭。然后细菌穿过内皮，在周围组织中增殖，最终扩散到羊水。感染模式与人类相似。本研究首次证明具核梭杆菌可能通过血液传播至胎盘并导致不良妊娠结局。这些结果加强了牙周病与早产之间的联系。我们的研究还表明，侵袭可能是具核梭杆菌感染胎盘的一种重要致病机制。
