Defining upper respiratory colonisation and microbiome evolution in mother-infant pairs following Neisseria lactamica inoculation in late pregnancy

Background: It is important to research new strategies to prevent serious infections in babies caused by bacteria living in the nose and throat. These bacteria are generally harmless, but in some circumstances cause infections of the lungs (pneumonia) and brain (meningitis), which are among the commonest causes of death in young children worldwide. Although vaccines protect against some forms of pneumonia and meningitis, they do not protect the very youngest babies (who are most at risk), and over 20% of the world's children do not receive all recommended vaccines. It is becoming harder to treat infections, because bacteria are becoming more resistant to antibiotics, and these resistant infections cause over 214,000 newborn deaths worldwide per year. Giving 'good' bacteria may be one way to reduce the risk of potentially dangerous 'bad' bacteria to babies. After birth, babies rapidly become covered (colonised) with bacteria from their mothers, other people and the environment. All the bacteria colonising a particular body site are called the microbiome. Many of these are 'good' bacteria, which can prevent 'bad' bacteria from colonising, and babies with certain 'good' bacteria in the nose and throat have fewer chest and ear infections. Scientists have tried giving probiotics ('good' bacteria swallowed or sprayed into the nose) to pregnant women, new mothers and babies. These studies show that probiotics are safe, but the amount of bacteria given is often unknown, and it is unclear if they work or how they affect the baby's microbiome. A more precise option is to use a controlled human infection study, where the amount of bacteria given is known. Our team has previously used controlled human infection to introduce Neisseria lactamica ('good' bacteria) into adult noses. This method safely and reliably decreases the amount of Neisseria meningitids ('bad' bacteria), but has not been tried in pregnant women or babies. Neisseria lactamica ('good' bacteria) is naturally found in over 40% of children aged 1-2 years, but is uncommon in adults and newborns. It does not cause infections: in fact, it may naturally protect against Neisseria meningitidis ('bad' bacteria). Proposed research: I will perform a controlled human infection study by introducing Neisseria lactamica ('good' bacteria) into pregnant women's noses, to find out if it is transferred to their babies after birth. This mimics the natural way that newborn babies become colonised with bacteria from their mothers. I will then study the nose and throat microbiome of the babies and their mothers. If the 'good' bacteria is detected in the babies, I will investigate how the population of bacteria changes over the first month of life in babies compared with their mothers. However, if this 'good' bacteria is not found in the babies, I will investigate if other types of 'good' bacteria have transferred naturally from the mothers to their babies. I have interviewed pregnant women when designing this study, and found that they support this proposal. Applications and benefits: This study will improve our understanding of how bacteria transfer from mothers to their babies, and whether controlled human infection in pregnancy can alter a newborn's developing microbiome. In the long term, the ultimate goal is to use 'good' bacteria to alter a baby's microbiome to prevent 'bad' bacteria from colonising and causing disease, especially in the highest-risk first month of life.