Investigating the Role of Bacteria and Immune Responses in Diagnosing Premature Birth Risk

The Importance of Bacteria in Human Health

A recent study aimed to explore whether bacteria and immune responses could serve as indicators for diagnosing the risk of premature birth. Throughout our lives, most of us have taken antibiotics. Physicians often recommend probiotics alongside antibiotics, which may seem contradictory. After all, antibiotics are meant to eliminate bacteria, so why introduce more?

Humans coexist with trillions of bacteria, which are crucial for maintaining health. While some bacteria are beneficial, often referred to as “good bacteria,” others can be harmful or “bad bacteria.” When we face an infection caused by harmful bacteria, antibiotics are prescribed to eradicate both good and bad bacteria. Probiotics, which are beneficial bacteria in pill form, are then taken to restore the good bacteria.

Understanding the Microbiome

The term “microbiome” refers to the diverse array of bacteria residing in specific body areas. The gut microbiome is the most studied, contributing significantly to food digestion. However, bacteria inhabit various body parts, including the skin, lungs, and vagina. A crucial question arises: if the immune system is designed to combat harmful bacteria, why doesn’t it attack beneficial ones?

For the immune system to function effectively, it must distinguish between “self” (the body’s own cells) and “non-self” (foreign entities). Epithelial cells create a barrier between the host’s internal cells and external bacterial cells. These cells are equipped with pathogen recognition receptors that identify bacterial presence. Upon recognizing good bacteria, epithelial cells produce small proteins known as antimicrobial peptides.

This continuous, low-level secretion of antimicrobial peptides constitutes physiological inflammation, which is asymptomatic. In contrast, when harmful bacteria are detected, epithelial cells release higher levels of antimicrobial peptides, attracting immune cells to the infection site to combat the bad bacteria. The immune system recognizes both helpful and harmful bacteria as non-self but varies its response intensity based on the type of bacteria detected. Each body part has a unique set of antimicrobial peptides tailored to manage specific bacteria in that area.

Immune Regulation of the Vaginal Microbiome

In the female reproductive system, the immune system faces a unique challenge: it must recognize the fetus as non-self without attacking it. To address this, the female reproductive tract is functionally divided into two compartments: the uterus, where fetal development occurs, and the vagina, which is exposed to the external environment.

Antimicrobial peptides in the vagina regulate the vaginal microbiome and protect the developing fetus from infections. If infections occur in the uterus, it is believed that harmful bacteria can migrate from the vaginal cavity through the cervix. An intrauterine infection can pose significant risks to both the mother and fetus, depending on the bacterial type, infection location, and size. Scientific evidence indicates that intrauterine infections are a leading cause of premature birth.

The Need for Improved Diagnostic Methods

Premature birth, defined as a baby being born before the 37th week of pregnancy, is the leading cause of death in newborns and children under five years old. Survivors of premature births face a heightened risk of neurobehavioral disorders, including cognitive deficits and cerebral palsy. Presently, diagnostic methods for predicting premature births are limited. The only preventive treatment available is progesterone, prescribed to women with a history of premature births or those with shortened cervixes during pregnancy. There is a critical need for accurate diagnostic tests in early pregnancy to identify at-risk women.

Study on the Vaginal Microbiome and Immune Response

Researchers in the USA recently published a study in *Nature Communications*, investigating whether they could analyze the vaginal microbiome and local immune response to assess the risk of premature birth. The study followed 432 women who carried their pregnancies to full term and 107 women who experienced preterm deliveries.

Vaginal swabs were collected during three prenatal visits, allowing scientists to characterize the types of bacteria present and the immune profiles of the samples.

Identifying Bacterial Types Linked to Premature Birth

The research team identified seven bacterial types associated with an increased risk of premature birth. They also discovered that the presence of an antimicrobial peptide called β defensin-2 could lower the likelihood of premature birth. Unique signatures of immune markers and bacterial species were linked to a higher risk of preterm delivery, requiring further validation. Nonetheless, the study holds promise for developing an accurate diagnostic tool.

The authors suggested that microbiome-based therapeutics, such as probiotics, and immune modulators could become potential preventive treatments. Jacques Ravel, Director of Genomics at the University of Maryland School of Medicine, stated, “Predicting prematurity has been a riddle that has troubled researchers and clinicians for years, but we are finally shedding light on a path toward offering treatment to women we can identify as being at risk.”

References

Gilbert, J. A. et al. Current understanding of the human microbiome. Nature medicine 24, 392 (2018).
Yarbrough, V. L., Winkle, S. & Herbst-Kralovetz, M. M. Antimicrobial peptides in the female reproductive tract: a critical component of the mucosal immune barrier with physiological and clinical implications. Human reproduction update 21, 353-377 (2014).
Witkin, S. S. The vaginal microbiome, vaginal anti‐microbial defence mechanisms and the clinical challenge of reducing infection‐related preterm birth. BJOG: An International Journal of Obstetrics & Gynaecology 122, 213-218 (2015).
Elovitz, M. A. et al. Cervicovaginal microbiota and local immune response modulate the risk of spontaneous preterm delivery. Nature communications 10, 1305 (2019).
Morrison, J. Bacteria and immunity in cervix may be key to predicting premature births (2019).