The DORMICe (Development Of the Respiratory Microbiota in Infants and children) study is a longitudinal study investigating how the microbiota in the upper respiratory tract develop over time. We recruited over 200 babies and have now followed them until they are 3 years of age.

We have visited our participants regularly at home through these first 3 years of life and have taken stool samples and throat swabs to monitor how the bacterial and viral communities in their upper respiratory tract and gastrointestinal tract develop over the critical early years. In addition to samples, we have collected information about illnesses, immunisations, feeding and environment at each home visit, so that we can relate this metadata to the microbiota.

We are using (i) next-generation sequencing to characterise the microbiota targeting the 16S rRNA gene common to all bacteria, and (ii) respiratory virus PCR to characterise the viral members of the community with our collaborators at Micropathology Ltd.

In addition to characterising the normal development of the children’s microbiota, we are focussing specifically on how the early microbial communities relate to the risk of wheezing in early life. We plan to continue following these children into their early school years to relate our findings to the development of asthma.

This study is in part funded by Micropathology Ltd.

Lead: Liz Powell

Crohn’s disease is an inflammatory bowel disease (IBD) of unknown cause and with no known cure which is becoming more common in children and adults. Crohn’s disease causes a great deal of suffering with abdominal pain, diarrhoea, bleeding and extreme fatigue. The gut microbiota are different in children with Crohn’s disease compared to those without, and the bacteria in the gut are believed to play a role in the development of the disease. Crohn’s disease is treated with immune-suppressing medications with potentially serious side effects.

At Chelsea and Westminster Hospital in the Department of Paediatric Gastroenterology (1) we are trialling a new diet for children with Crohn’s disease which is showing promise to prolong remission, reduce relapse and may offer children the chance to minimise medication use.
Our collaborative group (Professor Kroll and Dr Epstein) has previously shown that the gut microbiota is accurately represented by non-invasive sampling methods and that an invasive gut biopsy is not required (2).

We have recruited to date over 20 children with newly diagnosed Crohn’s disease and have characterised their faecal microbiota through next generation sequencing at serial time points in their treatment. We are correlating the microbiota with (a) diet; (b) disease activity and (c) IBD-specific quality of life scores.

The information generated will shed new light on our understanding of the role of the gut microbiota in Crohn’s disease, and specifically as it relates to diet. This will contribute to our understanding of how the disease develops and why diet is relevant to disease progress. It may allow us to predict in future which individuals are more likely to respond to dietary therapies at the outset.

The study is funded in part by the Crohn’s in Childhood Research Association (CICRA) (3), remains open and is continuing to recruit children with newly diagnosed Crohn’s disease. Chief Investigator: Dr Jenny Epstein, Paediatric Gastroenterologist.

Lead: Jenny Epstein

1. http://www.chelwest.nhs.uk/services/childrens-services/childrens-medicine/gastroenterology-nutrition-children
2. Assessing the Colonic Microbiota in Children: Effects of Sample Site and Bowel Preparation. Journal of Pediatric Gastroenterology and Nutrition. 2017 Feb;64(2):230-237. Shaw AG, Black N, Rushd A, Sim K, Randell P, Kroll JS, Epstein J.
3. http://www.cicra.org/

In the ‘Neisseriome’ project we are using a non-culture approach to investigate the dynamics of carriage of Neisseria species in infants from birth until they are 3 years of age. We are analysing oropharyngeal samples collected in the DORMICe study, PCR-amplifying rplF using Neisseria-specific primers, and sequencing the resulting amplicon libraries (Illumina MiSeq).

Our goal is to describe the pattern of Neisseria colonisation of infants, how this changes over time, and which early life events (feeding, viral infection, vaccination) affect the carriage of particular species. A particular interest is to establish what impact the new meningococcal group B vaccine, Bexsero, has on the carriage of Neisseria species in particular, but more generally on the composition of the whole upper respiratory tract microbiome. For this, we are analysing oropharyngeal samples collected from infants in their first year of life in the course of a vaccine study.

Lead: Roberto Fernandez Crespo

This study is in part funded by Meningitis UK.

The NeoM (Neonatal Microbiota) study was set up to look at the developing gastrointestinal microbiota in preterm infants. We recruited 369 babies and followed them through their stay on the neonatal intensive care unit (NICU).

We collected daily faecal samples alongside clinical data in order to characterise the evolving gastrointestinal microbiota and to understand the contribution of the microbiota to the development of the two conditions; necrotizing enterocolitis (NEC) and late-onset bloodstream infection.

Using next-generation sequencing to characterise the 16S rRNA gene in longitudinal faecal samples from the babies allowed us to discover two signatures that anticipated the development of NEC

1. a bloom of Clostridia perfringens and
2. persistently high levels of Enterobacteriaceae from birth.

We also found that infants who went on to develop late-onset bloodstream infection had a faecal bacterial community that did not follow the usual progression towards dominance by anaerobic organisms, and instead harboured high levels of either Staphylococcus or Enterobacteriaceae. We are currently investigating these signals in more depth with metagenomic analysis.

This study is in part funded by the Winnicott Foundation.

Leads: Alex Shaw and Kathy Sim

The NeoM2 follow-up study seeks to understand how the gastrointestinal microbiota of preterm infants changes in early childhood. A faecal sample from the participants was collected at the age of 2-3 years old and we are in the process of comparing these samples to those collected at birth. We will also compare our results to those obtained from the DORMICe study (our cohort of term infants), enabling us to determine if the gastrointestinal microbiota of preterm infants converges to that of a baby born at term by the time they are 3 years old.

This study is in part funded by the Winnicott Foundation.

Leads: Alex Shaw and Kathy Sim