Paediatric Microbiome Research Group

The paediatric microbiome research group

Agarose gel electophoresis of DNA samples with blue-light transilluminator imaging

Agarose gel electophoresis of DNA samples with blue-light transilluminator imaging

Faecal samples extraction and oropharyngeal swab viral analysis

Cataloguing faecal samples and oropharyngeal swabs

Configuring a PCR (Polymerase Chain Reaction) machine

Configuring a PCR (Polymerase Chain Reaction) machine

Inoculating a 96-well plate with culture medium using a multichannel pipette

Inoculating a 96-well plate with culture medium using a multichannel pipette

Inoculating a blood agar plate in the biological safety cabinet

Inoculating a blood agar plate in the biological safety cabinet

General enquiries


Section Secretary
Jane Webb

jane.webb@imperial.ac.uk
+44 (0)20 7594 3990

Research publications

The paediatric microbiome research group has embraced next generation sequencing technologies to achieve its main aim of understanding the development of the respiratory and gastrointestinal microbiota in term and premature infants and how the early microbiota relates to current and future health. We have productive collaborations with Dr Lindsay Hall (Inst. of Food Research and U. East Anglia), Professor Saheer Gharbia (Public Health England), Dr Ron Dixon (University of Lincoln), Prof Adnan Custovic (Imperial College London), Dr Jenny Epstein (Chelsea and Westminster NHS Trust), and Dr Colin Fink (Micropathology Ltd).


Research cohorts

The group has established two cohorts; one of 369 infants recruited at premature birth (<32 weeks gestation), admitted to the neonatal units of Imperial College NHS Trust (the NeoM study); and the second, 220 healthy infants recruited at term, born at St Mary’s Hospital (the DORMICe study). With Dr Epstein (paediatric gastroenterologist), we are studying a further patient group, of young people with inflammatory bowel disease.

From our premature cohort, we have established a signature of dysbiosis preceding the diagnosis of necrotising enterocolitis and a delayed maturation of the gut microbiota in the case of late onset blood stream infection. We are exploring this dysbiosis further by exploring the clostridial component of the microbiota using targeted culture techniques, toxin analysis and whole genome sequencing. We are utilising metagenomics to understand in more depth the microbial involvement in the pathogenesis of necrotizing enterocolitis. In a continuation study (NeoM2) we are following the cohort to school age to establish how their gut microbiota develops further.

The DORMICe study is focusing initially on the development in tandem of the respiratory and gastrointestinal microbiota, as well as the upper respiratory tract (URT) virome, to the age of 3 years. We have a particular interest in the relationship of the microbiota to the development of wheezing in early life. In a parallel study, we are monitoring the colonisation of the URT with Neisseria species, as part of a larger study relating to immunisation against meningococcal disease.

We are grateful to the families, our collaborators and our funders for supporting our research.


Research group members


Our group focuses on five core areas - expand the sections below to find out more about each of our studies and research themes:

Research areas

DORMICe study (Development Of the Respiratory Microbiota in Infants and children)

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

MEDIC study (Microbial effects of an Exclusion Diet In Crohn’s disease)

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/

Neisseriome

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.

NeoM study

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

NeoM2 study

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