Dr Charlotte Burford
Looking at modulating intestinal microbiome and stool microbiome in Biliary Atresia paediatric patients.
F1/F2 Research Awards Winner:
“Jejunal Mucosal Microbiome in Biliary Atresia.”
Biliary Atresia (BA) is the most common reason for paediatric liver transplantation, Dr Burford explains. This is a disease characterised by obliteration of the biliary tree which presents with jaundice in early infancy. Only about 60% of infants who have surgical intervention will have their jaundice cleared. However, liver cirrhosis can still bring associated complications which require liver transplantation.
Dr Burford explains:
“‘Despite the significant impact of this disease, the mechanisms behind why it occurs remain unclear. Over the last decade, there is a growing body of evidence suggesting that the gut microbiome may play a role in the pathogenesis of Biliary Atresia. Research already completed at King’s College Hospital has shown a lower relative abundance of ‘good’ Bifidobacterium in BA patients with a higher relative abundance of potentially ‘bad’ bacteria such as Enterococcus, Clostridium and Haemophilus.
However, whilst these results have not demonstrated a significant difference in bacteria between outcomes in BA patients (i.e. LT vs no LT) evidence from other diseases (both liver and non-liver) has shown a difference between the intestinal microbiome and the stool microbiome.
In this study we will use intestinal samples already collected from 15 BA patients and 5 non-BA controls to sequence the intestinal microbiome. We will compare this to the data on the stool microbiome we already have and between outcome groups.”
Dr Burford then describes how the study has three key aims:
- to compare the stool and jejunal mucosal microbiome in Biliary Atresia infants at both KPE and LT
- to characterise changes in the jejunal mucosal microbiome between KPE and LT
- to identify potential associations between the jejunal mucosal microbiome at KPE and short term clinical outcomes (including 6 months jaundice clearance, 1 year native liver survival, incidence of cholangitis and development of portal hypertension), as well as biomarkers of liver disease severity in BA
She then goes onto describe her hypothesis:
“The hypothesis would be that the jejunal mucosal microbiome would be significantly different to the stool microbiome and that the proximity of the jejunum to the site of liver inflammation would provide a more accurate reading of the microbiome and clinical outcomes in BA. The comparison between the KPE and LT microbiomes would help to determine the most effective way of modulating the microbiome via more targeted microbiome therapy, for example appropriate use of antibiotics or probiotics to improve outcomes in BA, potentially reduce the percentage of patients suffering liver deterioration and/or requiring liver transplantation.”
I am very honoured and incredibly grateful to have received this award. I have become fascinated with the role of the microbiome in biliary pathology since starting work with Dr Jain. This award allows me to continue to contribute to that amazing work and explore a novel approach to BA pathogenesis which has huge potential implications for patient care. I am also excited by the new research skills I will be able to develop, including a deeper understanding of bioinformatics.
As a less than full time trainee with three children, winning this award has had huge significance for my academic clinical career. I am thankful to Dr Falk and Guts UK for believing in me and this project and to Dr Jain for tirelessly supporting me over the last seven years. I am really looking forward to continuing my work with the fantastic team at King’s!- Dr Charlotte Burford