Abstract: Abnormal immune responses to the resident gut microbiome can drive inflammatory bowel disease (IBD). We combined high-resolution, culture-based shotgun metagenomic sequencing and analysis with matched host transcriptomics across three intestinal sites (terminal ileum, cecum, rectum) from pediatric IBD patients and matched controls to investigate this relationship. Combining our site-specific approach with bacterial culturing, we establish a cohort-specific bacterial culture collection, comprising 6,620 isolates (170 distinct species, 32 putative novel), cultured from 286 mucosal biopsies. Phylogeny-based, clade-specific metagenomic analysis identifies key, functionally distinct Enterococcus clades associated with either IBD or health. Strain-specific in vitro validation demonstrates differences in cell cytotoxicity and inflammatory signaling in intestinal epithelial cells, consistent with the colonic mucosa-specific response measured in patients with IBD. This demonstrates the importance of strain-specific phenotypes and consideration of anatomical sites in exploring the dysregulated host-bacterial interactions in IBD.

Biography: Ed Giles is a consultant paediatric gastroenterologist at Monash and the Royal Children’s Hospital in Melbourne and lead for inflammatory bowel disease at Monash. Ed trained at the University of Melbourne and the Royal Children’s Hospital, and several hospitals in London. He received a PhD from the University of London in 2015. He was a consultant at the Royal London Hospital and Barts Medical School until he returned to Melbourne in 2016.

He is a research fellow at the Hudson Institute of Medical Research and senior lecturer in the department of paediatrics at Monash University. He has held a number of senior positions, including past president of the Australasian Society of Paediatric Gastroenterology, Hepatology and Nutrition and foundation chair of the Gastroenterological Society of Australia – Paediatric Network. His research interests are in host-microbiome interactions, particularly in IBD. He has projects developing novel biotherapeutics, and collaborations in laboratory research for which he jointly holds several grants worth over AUD$9 million. He has published widely, including in Science, Science Translational Medicine and Nature Reviews Microbiology. He is also involved in clinical research and is PI on several industry clinical trials.