“I look after young people living with obesity. Obesity affects 30% of children by Year 6. Obesity has a lot of nutritional drivers and much of the management therefore centres on nutrition,” says Dr Emma Webb, a Consultant Pediatrician at the Norfolk and Norwich University Hospitals.

Emma has teamed up with Professor Arjan Narbad’s group here at the Quadram Institute to work on a Clinical Seedcorn project investigating the gut microbiome in children living with obesity and if their gut microbes affect responses to treatment.

“There’s some research that suggests that adults living with obesity have a less diverse microbiome and there’s some evidence to suggest that that’s the same in children. I decided to reach out to researchers here at the Quadram Institute who have that expertise to collaborate, learn more and see if there’s a potential for future treatments,” says Emma.

Emma is working with Professor Arjan Narbard who is an expert on the gut microbiome.

Arjan explains how the collaboration began, “Normally when we have a research idea we try to find clinicians to work with, but this was the opposite. Emma actually contacted me. We started chatting and then the Clinical Seedcorn opportunity came up. We wanted to look at the link between the diet, the microbiome and obesity markers.”

Sampling the microbiome in children with obesity

The team received a grant from the Clinical Seedcorn fund, jointly funded by the Quadram Institute and the Norfolk and Norwich Hospitals Charity for a study to explore the gut microbiome in childhood obesity.

“The Clinical Seedcorn grant was to look at what the microbiome looks like in kids that arrive in my clinic and what the impact of any treatments might be on the microbiome. It’s a pilot study to see whether we can design an intervention in the future,” says Emma.

Participants who consented to be part of the study gave stool samples to allow researchers to study the gut microbiome.
Arjan explains, “We analyse the gut microbiome in two ways. We do shotgun metagenomics which sequences everything in the microbiome and that allows us to the see the composition of gut microbes and how they differ between individuals.”

He continues, “At the same time we do metabolomics. Using the same stool sample, we perform proton NMR. With metabolomics we can look at thousands of metabolites and see if metabolite levels change with or without treatment. Combining the information from the metagenomics and metabolomics is really powerful.”

Dr Jacob Dehinsilu is a Research Scientist in the Narbad group working on analysing the data. He remarks, “There aren’t many European or UK obesity cohorts like this. So far, most of these studies are based in the USA, India, China or Mexico so it’s filling a gap in our knowledge.”

He adds, “The age range of our study is quite unique too. Most pediatric studies looking at the gut microbiome are on teenagers or infants, whereas our study includes participants aged from 3 to 17.”

A challenge of the study has been that as the study is focused on children living with obesity, they do not currently have a control group of children of healthy weight to compare to, but the team have a solution.

“We had the idea to take publicly available data, build our own healthy control in silico and then process this data through the same pipelines to see if there are any differences between the gut microbiome of children living with obesity compared to healthy children,” explains Jacob.

Does the gut microbiome impact the effectiveness of treatment?

Emma points out another aspect of the Clinical Seedcorn project, “We are looking at what the impact of any treatments we give are, whether that’s diet or medication, on the gut microbiome.”

Emma explains, “As part of our clinical routine we now look at micronutrients, as hidden hunger is common in children living with obesity.”

Arjan continues, “It’s important to understand the impact of micronutrient deficiency on the gut microbiome. We’re looking at how the gut microbiome of children changes before and after the dietary intervention.”

Analysis of the gut microbiome data is underway. Jacob says, “There are correlations between certain bacteria and certain vitamins. Initial results show statistically significant differences between in silico controls and those living with obesity in terms of gut bacterial diversity and the relative abundance of 38 species.”

Building a base for future research and collaborations

A key aim of the Clinical Seedcorn fund is to spark new collaborations and projects.

Arjan explains, “The cohort of this study is quite small so it won’t give us definitive answers but it is providing preliminary data as a baseline for a bigger grant. It’s very exciting research. It is great that the fund encourages new collaborations between clinicians and bioscience researchers.”

He continues, “I’ve had experience working with clinicians for at least ten years, but my previous experience has been more focused on infection control and pathogens. This Clinical Seedcorn funding has allowed us to make a new clinical collaboration with Dr Emma Webb.”

Jacob reflects on his experience working with clinicians as part of the project, “It’s rewarding working with clinicians. Rather than just getting vials or sheets of data we learn more about the real world aspect. It makes you more motivated and engaged in research.”

Emma describes her experience, “Because of the Clinical Seedcorn project, my collaborations have expanded and evolved.”

Emma is now also working with Professor Martin Warren on a project focused on micronutrients in obese children, as well as working with Dr Maria Traka and an interdisciplinary group across the Norwich Research Park to develop dietary interventions in schools.

She concludes, “That’s a strength of the Quadram Institute building, when you’re here it’s easy to meet other people.”