Fusobacterium nucleatum can cause pregnancy complications including preterm birth, neonatal death, and stillbirth. However, compounds found in fish oil can prevent these complications in mice when they are caused by the oral bacteria, according to researchers at the Columbia University College of Dental Medicine and Vagelos College of Physicians & Surgeons, who now suggest a new strategy for protecting pregnancies.
About one in 10 infants in the United States are born before term, the researchers report, and between 10% and 30% of preterm births have been attributed to uterine infections caused by F nucleatum. In pregnant women, the placenta is at particular risk for infection by the bacteria.
“This type of bacteria is ubiquitous. Everybody has it in their mouths,” said Yiping Han, PhD, professor of microbial sciences in dental medicine at the Columbia University College of Dental Medicine and of microbiology and immunology at the Columbia University Vagelos College of Physicians and Surgeons, as well as senior author of the study. “The problems start when it travels to other parts of the body.”
Hormonal changes during pregnancy can cause inflammation and bleeding in the gums, which affects between 30% and 100% of pregnant women, according to the researchers. Bleeding gums create an entryway for the bacteria to leak into the bloodstream. Once in the circulatory system, the bacteria can migrate to the placenta and cause inflammation there, sometimes triggering miscarriage or stillbirth.
“We know from our previous work that uterine inflammation due to infection with this bacteria is associated with adverse pregnancy outcomes, but in order to prevent those outcomes, we needed to determine exactly how these infections trigger inflammation,” said Han.
The researchers injected the bacteria into mice during their third trimester of pregnancy. As predicted, the bacteria invaded the animals’ uteruses. The bacteria then triggered an inflammatory response in endothelial cells within the placenta, leading to preterm births. The response only occurred when a specific immune protein was in the mothers’ endothelial cells.
In pregnant mice lacking this protein, fewer fetuses died, suggesting that inflammation ignited by the protein is crucial for causing preterm births. After determining how the bacteria trigger inflammation within the placenta, then, the researchers used cultured cells to look for ways to inhibit those mechanisms.
“We were looking for an anti-inflammatory agent that’s safe for pregnant women to use,” said Han.
Omega-3 fatty acid supplements are widely used to reduce inflammation in chronic inflammatory diseases such as heart disease and rheumatoid arthritis, prompting the researchers to consider fish oil, which is rich in omega-3 fatty acids. These supplements already are recommended for pregnant women to support fetal development.
The research showed that supplements that included omega-3 fatty acids also inhibited inflammation and bacterial growth in pregnant mice. They also reduced preterm births, miscarriages, and stillbirths. The researchers now hope to begin a clinical trial to test whether omega-3 fatty acids can prevent intrauterine F nucleatum infection and adverse outcomes in pregnant women.
The researchers note, however, that the doses of omega-3 fatty acids used in the study were far higher than those recommended for people taking fish oil supplements. They also say that while the study points to a promising avenue for future research, it does not support any immediate changes in clinical practice.