P245 Dynemics of the Immune-transcriptome and Microbiome in Paediatric Inflammatory Bowel Disease
Elawad, M.A.(1);Kumar, M.(2);Saadaui, M.(3);Elhag, D.(3);Akobeng, A.(2);Al-Mudahka, F.(2);Hendaus, M.(4);Al Khodor, S.(3);
(1)Sidra Medical and Research Centre, Department of Paediatric Gastroenterology, Doha, Qatar;(2)Sidra Medicine, Department of Paediatric Gastroenterology, Doha, Qatar;(3)Sidra Medicine, Research Department, Doha, Qatar;(4)Sidra Medicine, Pediatrics Department, Doha, Qatar;
Background
Inflammatory Bowel Disease (IBD), including Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) is characterized by a chronic relapsing inflammation of the gastrointestinal tract, resulting from the complex interplay between genetic make-up, microbiome, environmental factors, and immune response. The potential role of the immune response and microbiome in the development and progression of IBD has been extensively studied, however, markers that can predict disease relapse remain scarce, especially in children with IBD. Developing non-invasive monitoring tools are also extremely needed in the field.
Methods
Multi-omics analysis provides a global view of changes in immune, microbial, and environmental factors. In this study, we enrolled a total of 85 IBD patients and 57 matching controls living in Qatar and attending Sidra Medicine IBD clinic. Patients were followed- up every 3 months and when they felt unwell. In addition to the phenotypic and clinical data, saliva, blood, and stool samples were collected at each visit. Salivary and gut microbiome analysis was performed using high throughput 16S rRNA gene sequencing. Blood samples were stimulated with a total of 14 ligands before being processed for immune transcriptomics and proteomics . Patients were compared to their matching healthy controls.
Results
Reduced microbial diversity and increased variability in the microbiome composition was observed in both CD and UC patients compared with controls. Our preliminary data show that Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria are the common phyla present in both patients and controls. Interestingly, the longitudinal microbiome analysis revealed reduced temporal microbial stability in both CD and UC patients, particularly in patients with changes in disease activity. The microbiome composition of patients in remission appeared similar to healthy controls, whereas dysbiosis was mostly observed in patients with increased disease activity. We then characterized the spectrum of transcriptional responses in blood collected from healthy controls and IBD patients stimulated for 6 hours with 14 ligands. Blood transcriptomics analysis separated patients from controls and a clear clustering was observed when the same patient was in relapse or remission. We aim to identify microbial and immune signatures that can classify patients CD, UC and IBD-U and predict onset of both remission and relapse.
Conclusion
This is the first paediatric data to show that, by integrating various multi-omics datasets collected from CD, UC and IBD-U patients and comparing their profiles with their matching controls, we are able to identify specific non-invasive predictive markers for disease remission and relapse.