Microbiome

What we do

We are undertaking a wide range of multidisciplined studies that are designed to determine how the microbiome and its interactions with the maternal host change throughout pregnancy. We do this using a combination of classical biochemistry methods and “systems” approaches whereby data acquired from genomic, transcriptomic and metabolic profiling platforms are integrated and modelled. It is hoped that this will lead to better understanding of the mechanisms underpinning pathologies in pregnancy and improved diagnostic and predictive tools that will assist in patient stratification and ultimately, improved outcomes for mother and baby.

Why it is important

Preterm birth occurs globally in 10% of pregnancies and is the leading cause of death in children under 5 years of age. Although there can be many causes of preterm birth, microorganisms that cause infection and inflammation in the reproductive tract are associated with around 40% of all preterm birth cases.

The “microbiome” is a term that describes the collection of microorganisms (bacteria, fungi and viruses), their genetic material as well as the surrounding biological and chemical environment that they live in. Advances in sequencing technologies that allow us to identify and compare levels of microorganisms in different samples show that different body sites are home to different microbiomes. This includes the reproductive tract of women.

The composition of the microbiome can be influenced by genetics, nutrition, environment, lifestyle, medications, and other host factors. The vaginal microbiome varies widely among healthy, asymptomatic women of reproductive age, and studies have additionally shown that the vaginal bacterial composition varies among different ethnic groups. Studies of the vaginal microbiome in pregnant and non-pregnant women showed that the vaginal bacteria naturally undergo marked decrease in species diversity as the pregnancy progresses. We have recently shown that certain bacteria in the reproductive tract confer risk of preterm birth, while others offer protection. The mechanism by which these species influence risk of preterm birth requires further investigation. We are also interested in understanding how microbiomes at different body sites can interact with each other and with the maternal immune system and how these interactions might be linked to increased risk for preterm labour and delivery. Further understanding of how microbiome-maternal host interactions influence earlier pathologies in pregnancy (e.g. miscarriage) also warrant investigation.

Impact

We have shown that women with a short cervix in the second trimester of pregnancy, which is a risk factor for preterm birth, have higher levels of a bacteria called Lactobacillus iners in their reproductive tract compared to those with a regular length cervix. Dominance of the reproductive tract by L. iners is also a risk factor for preterm birth. In contrast, women who have a regular length cervix and deliver at term, maintain high levels of a related bacteria, Lactobacillus crispatus, throughout their pregnancy. Modulation of the vaginal microbiome towards a protective bacterial community structure may prove to be a useful strategy for preventing preterm birth.

We have also recently undertaken a series of studies to assess what impact different treatments for preterm birth prevention have on the composition of bacterial communities in the reproductive tract. Our findings suggest that vaginal progesterone for the prevention of preterm birth has no negative impact on bacterial profiles, which is reassuring to patients and clinicians. Similarly, the use of a nylon, monofilament suture for cervical cerclage has minimal impact upon the vaginal microbiome. However, the use of braided sutures for cervical cerclage can lead to increased abundance of potentially pathogenic bacteria in the vagina, increased inflammation and premature remodelling of the cervix. This is associated with increased rates of neonatal loss and preterm birth when compared nylon cerclages.

Additional studies with collaborators are investigating how microbial-host interactions may influence other areas of reproductive health including miscarriage, ectopic pregnancy and cervical cancer.

Summary of current research

• The role of vaginal microbiota in preterm birth and preterm premature rupture of membranes (PPROM) led by Dr David MacIntyre
• Reproductive tract inflammatory activation by bacterial metabolites led by Dr David MacIntyre
• Stratification of pregnancy outcome and preterm birth risk using microbial profiling led by Dr David MacIntyre and Prof Phillip Bennett
• Characterisation of maternal immune-microbiome interactions led by Dr Lynne Sykes, Dr David MacIntyre and Prof Phillip Bennett
• The role of vaginal microbiota in the pathogenesis of cervical cancer led by Dr Maria Kygiou
• Vaginal microbiota and early pregnancy outcomes led by Dr David MacIntyre, Prof Phillip Bennett and Prof Tom Bourne

Lead researchers